IndraLab

Statements

TP53 is modified

| 2 988

TP53 is methylated. 10 / 830

| 2 828

sparser

"Other biomarkers including epithelial VEGF, p53, Ki-67, cyclin D1, and p16 promoter methylation) were not associated with the outcome."

23771133

➶

sparser

"Similarly, PRMT5-mediated p53 arginine methylation results in preferential p21 transcription as opposed to apoptotic genes [ xref ]."

33199193

➶

sparser

"Taken together, these results strongly suggest that SCF Fbxo22 -KDM4A targets methylated p53 for ubiquitin-dependent protein degradation."

26868148

➶

sparser

"For example, the crosstalk between serine phosphorylation and lysine methylation of the mitochondrial protein DAM1 and the transcription factor p53 has been described in human cancer cells (Fischle et al. xref ; Zhang and Dent xref )."

33666740

➶

sparser

"It has been reported that intragenic TP53 methylation differs between normal and transformed human colorectal cancer cell lines [ xref ]."

33603167

➶

sparser

"One possibility is that JMJD3 contributes to the regulation of p53 methylation, as previously suggested using an antibody raised to methylated lysine xref , but not confirmed in an independent study xref ."

24797517

➶

sparser

"In that category, the most sensitive and specific biomarker (more properly, “biosignature”) for detecting ovarian cancer currently appears to be a panel of six serum proteins (leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor and CA125), which has been reported to identify ovarian cancer as early as stage I with a striking 99.3% positive predictive value and 99.2% negative predictive value. xref The second biomarker category aims to predict outcome; examples include p53, p21, Ki-67, and HOXA11 DNA methylation. xref – xref The third category is similar to the second but specifically aims to predict which patients will respond to a particular treatment, as is the case for the biomarker upon which this review is focused."

19209300

➶

sparser

"Therefore, the arginine methylation of p53, KAT3B, or other p53 co-factors may play a significant role in the differential regulation of p53 target genes in response to a particular stress signal."

18581285

➶

sparser

"Similarly, it has been reported previously that lysine methylation on p53 protein mediated by SET7/9 was not a target of LSD1 xref ."

26902152

➶

sparser

"It would also be of interest to examine how cytosine methylation at the 5′-C of the CpG sites at Fapy•dG 248 and 273 may influence replicative bypass of Fapy•dG, as we have shown previously that in p53 codon 273 cytosine methylation increases MF of a bulky dG adduct significantly [ xref ]."

34464900

TP53 is methylated on K372. 10 / 58

| 58

➶

sparser

"We also show that reduced PRMT5 expression leads to cyclin D1 transcriptional repression via loss of TP53K372 methylation, which results in decreased BCL3 expression and enhanced recruitment of NF-κB p52-HDAC1 repressor complexes to the cyclin D1 promoter."

24189068

➶

sparser

"A dynamic sequential relationship exists between p53K372 methylation and p53 acetylation, with DNA damage increasing SET9-mediated p53K372me1 levels and this in turn promoting acetylation."

21826189

➶

sparser

"KDM3A was found to impede the methylation of p53K372, which subsequently restricted the activity of p53 and the expression of p21."

33816782

➶

sparser

"In contrast, SET7/9-catalyzed p53K372 methylation adopts an extremely early S N 2 TS with the short 2.0 Å C–S distance and the long 2.3 Å C–N distance (the S–N distance around 4.3 Å, xref )."

31034218

➶

sparser

"The latter may be due to JMJD1A-mediated reduction of lysine 372 methylation on TP53, a methylation mark known to increase TP53 stability and nuclear localization."

32605929

➶

sparser

"Several studies have demonstrated that Set7/9-mediated methylation of p53-K372 facilitates acetylation of the adjacent lysine residues (K373 and K382) in p53 [ xref , xref ]."

24298606

➶

sparser

"In order to improve our understanding of the Smyd2 catalytic cycle, here we carried out μ‐second MD simulations of the following systems (see Fig. xref ): Smyd2 in complex with AdoMet cofactor (Model‐A); Smyd2‐AdoMet‐p53 peptide (unmethylated) complex (Model‐B); Smyd2‐AdoHcy‐p53 peptide (methylated at Lys370) complex (Model‐C); and Smyd2‐AdoMet in complex with the p53 peptide methylated at Lys372 (Model‐D)."

31069954

➶

sparser

"Set7 mediated methylation of Lys372 in P53 increases its stability, resulting in the induction of P53 target genes ( xref )."

27146893

➶

sparser

"Previous report suggested that mono methylation of p53 at K372 enhances the transcriptional activity by stabilizing the chromatin bound p53. xref Therefore, we quantified the p53 occupancy on p21 promoter by chromatin immunoprecipitation (ChIP) assay."

27694900

➶

sparser

"For example, methylation of p53 K372 depends on the addition of an acetyl moiety on neighboring lysine residues (Kurash et al , xref )."

24714364

TP53 is methylated on K370. 10 / 45

| 45

➶

sparser

"This inhibitor clearly suppressed p53K370 methylation mediated by SMYD2 in lung carcinoma A549 cells."

26751963

➶

sparser

"Similarly, the mechanism underlying the repressive effect of methylated p53-K370 needs further investigation."

18581285

➶

sparser

"In addition, the histone demethylase LSD1 specifically removes mono- or di-methylation at K370 of p53 to repress p53-mediated transcriptional activation [ xref ]."

29755654

➶

sparser

"As shown in xref D , significant reductions in p53 Lys 370 methylation occurred by 18 h following LLY-507 treatment of SMYD2-overexpressing KYSE-150 cells."

25825497

➶

sparser

"Furthermore, in response to DNA damage, the level of methylated p53-K370 associated with the p21 promoter is decreased."

18581285

➶

sparser

"Although the site of Smyd2-mediated methylation on the p53 protein at lysine 370 has already been discovered, the authors have shown that the methylation status of p53 at K370 does not affect binding of p53 to its target promoters."

33824417

➶

sparser

"Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase, which has been shown to repress p53-mediated apoptosis in response to various types of DNA damage by methylation of the transcription factor p53 at lysine 370 [ xref , xref ]."

25014164

➶

sparser

"The p53 peptide methylated at Lys370 exhibits higher mobility compared to the unmethylated or methylated at Lys372 one."

31069954

➶

sparser

"Recently LSD1 was shown to repress p53-mediated transcriptional activation by removing methylation at K370 of p53 ."

18501190

➶

sparser

"SMYD2 catalyzes the methylation of the p53 protein at lysine 370, which represses p53-dependent transcription ( xref )."

27334938

TP53 is methylated on K382. 10 / 24

| 24

➶

sparser

"Methylation of p53 at lysine 382 leads to decreased apoptosis either through decreased transcriptional activation by antagonizing p53 acetylation, or by promoting p53 ubiquitination for degradation xref ."

| PMC

➶

sparser

"Similarly, dimethylation of the R located at the -3 position also reduced methylation of p53 K382 which had been shown previously to be methylated by SET8."

22583696

➶

sparser

"However, H4K20 is not the only target of PR-Set7 as the tumor suppressor protein p53 is also methylated at lysine residue 382 resulting in suppression of p53 dependent transcriptional activation ( xref )."

21035370

➶

sparser

"We demonstrate that SET8-mediated methylation of p53 at Lys-382 promotes the interaction between L3MBTL1 and p53 in cells, and the chromatin occupancy of L3MBTL1 at p53 target promoters."

20870725

➶

sparser

"53BP1 and L3MBTL1 both bind to methylated H4K20 and p53K382, raising the idea that sequences in non-histone proteins have evolved to mimic histone sequences and might therefore be regulated by conserved reader domains [ xref , xref , xref , xref - xref ]."

24561874

➶

sparser

"We chose to inactivate the methyl-transferase SET8, which has been shown to mediate the inhibitory methylation of p53 at K382 ( xref )."

20598361

➶

sparser

"Recent studies revealed that p53K370, K372 and K382 can also be methylated, indicating cross-regulation between acetylation, methylation and ubiquitynation."

21371315

➶

sparser

"P53 methylation at K370, K372, K373, and K382 by the PKMTs SETD7 xref , SMYD2 xref and SETD8 xref , SETDB1 xref , GLP/G9A xref suppresses p53 transcriptional activity in several cancer cell line models, including lung, kidney, and bone."

30683849

➶

sparser

"In addition, recent work by West et al . has implicated the L3MBTL1 protein as a ‘reader’ for both the p53 Lys382 methylation and H4K20me marks and in this capacity serves as a regulator of the downstream p21 and PUMA transcript levels (West et al ., xref )."

28514051

➶

sparser

"Indeed, the methylation of p53 at K382 prevents p53 binding to p21 and PUMA promoters."

18581285

TP53 is methylated on lysine. 10 / 12

| 12

➶

sparser

"Mono- or di-methylation of TP53 at four C-terminal lysine residues by at least six different lysine methyltransferases facilitates binding by TIP60, PHF20, L3MBTL1 and 53BP1 to TP53 ( xref , xref , xref ) ( xref ; xref )."

24395704

➶

sparser

"To further the analogy to histone modification, the same p53 lysine residues that are methylated are also subject to other modifications like acetylation, sumoylation and ubiquitylation [ xref ]."

18923809

➶

sparser

"P53 is methylated at C-terminal lysine residues: K370, K372 and K382."

24797517

➶

sparser

"For example, methyltransferase Set 9 can specifically methylate lysine residues in p53 to regulate its target gene expression [ xref ]."

29986538

➶

sparser

"To this point, three different methyltransferases have been shown to be able to methylate C-terminal lysine residues of p53."

19450511

➶

sparser

"These results disfavour a role for JMJD3 in the regulation of p53 C-terminal methylation, however, we cannot rule out that JMJD3 is involved in regulating p53 methylation at other lysine residues than the tested ones, or that additional co-factors are required for an efficient enzymatic removal of methylation."

24797517

➶

sparser

"The p53 protein is methylated at lysine residues in its C-terminal regulatory region p53, which stabilizes it, restricts it to the nucleus, and enhances its ability to transcriptionally transactivate target genes (reviewed in xref )."

33193732

➶

sparser

"Interestingly, some lysine residues of p53 that are modified by acetylation can also be methylated [ xref ]."

28208785

➶

sparser

"Genotoxic stress can induce methylation of p53 in at least three different lysine residues, which mediate activation or repression of p53-dependent apoptosis ( Chuikov et al., 2004; Huang et al., 2006[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

20603083

➶

sparser

"Some HMTs (SETD8 and SMYD2) have been found to regulate the methylation of non-histone proteins in particular p53 in lysine residues."

30834247

TP53 is methylated on K373. 10 / 11

| 11

➶

sparser

"In addition, G9a (also known as EHMT2) and GLP (also known as EHMT1), which share 80% sequence homology in their respective SET domains [ xref , xref ], have been found to methylate p53 at K373, correlating with inactivation of p53 [ xref ]."

21966347

➶

sparser

"P53 Methylation at K370, K373, and K382 suppresses p53 transcriptional activity, whereas methylation at K372 facilitates its activity."

33462212

➶

sparser

"In general, while methylation of p53 at K370, K373 and K382 represses p53 transcriptional activities, methylation at K372 enhances p53 activities. xref – xref Since KDM3A knockdown activated the expression of p53-dependent genes, we reasoned that increasing p53 methylation enhanced its transcriptional activities."

27270439

➶

sparser

"Two KMTases, G9a and Glp, responsible for K373 methylation of p53, also catalyse mono and di-methylation of H3K9 and mono-methylation of H3K27 [ xref ]."

24298606

➶

sparser

"Much like methylation of K373 in p53, G9a-mediated methylation of H3K9 leads to transcriptional repression [ xref ]."

24298606

➶

sparser

"However, is still unclear whether this cellular effect is a direct result of p53 K373 methylation, or whether it is caused by repressive methylation of histones in the promoters of pro-apoptotic target genes."

24298606

➶

sparser

"Genetic knockdown of G9a inhibits cancer cell growth and the di-methylation of p53 K373 results in the inactivation of p53."

20614940

➶

sparser

"G9a is indeed responsible for p53 methylation at lysine 373, and this form of the transcription factor was observed to be inactive ( xref )."

26441991

➶

sparser

"It has been shown that in the absence of exogenous stimulation, spontaneous/endogenous stress can induce deacetylation and methylation at K373 and K382 of p53, and this suppresses the transcriptional activity of p53, and the resulting p21 gene expression."

28208785

➶

sparser

30683849

TP53 is methylated on R333. 3 / 3

| 3

➶

sparser

"The methylation of p53 at arginine 333, 335 and 337 by PRMT5 was independently validated and shown to suppress p53-mediated target gene expression and apoptosis ( xref )."

33637564

➶

sparser

"The type II protein arginine transferase, PRMT5, interacts with and methylates p53 at R333, R335 and R337 following DNA damage [ xref ]."

26425661

➶

sparser

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage ( xref )."

21975038

TP53 is methylated on R337. 2 / 2

| 2

➶

sparser

"The type II protein arginine transferase, PRMT5, interacts with and methylates p53 at R333, R335 and R337 following DNA damage [ xref ]."

26425661

➶

sparser

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage ( xref )."

21975038

TP53 is methylated on arginine. 2 / 2

| 2

➶

sparser

"Lysine (K) and arginine (R) residues in p53 can be methylated, and a growing number of studies in recent years have shown that p53 methylation takes place during the DNA damage response. xref – xref Methylation of lysine and arginine residues in histones has long been known to impact chromatin structure and gene expression. xref In recent years, the methylation of p53 has emerged as an important modification that affects its function in various processes, such as cell cycle arrest, DNA repair, senescence, apoptosis, and tumourigenesis. xref Whether p53 is activated or depressed depends on the location of the modification and the number of methyl groups attached. xref Protein arginine N -methyl transferase 5 (PRMT5) was first shown to methylate p53 at several arginine residues (R333, R335, and R337) in the tetramerization domain, xref which specifically controls the functions of p53 in cell cycle arrest and is suggested to inactivate p53 during lymphomagenesis. xref , xref There are three different lysine methyl transferases (KMTs) that could mono-methylate p53, and there are at least two KMTs could di-methylate p53. xref "

32532965

➶

sparser

"Methylated p53 arginine residues affect p53 response by influencing the specificity of p53 binding to promoters [ xref ]."

35205407

TP53 is methylated on R335. 2 / 2

| 2

➶

sparser

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage ( xref )."

21975038

➶

sparser

"The type II protein arginine transferase, PRMT5, interacts with and methylates p53 at R333, R335 and R337 following DNA damage [ xref ]."

26425661

TP53 is methylated on K305. 1 / 1

| 1

➶

sparser

"KMT2A-D and KMT2G have been shown to be capable of methylating p53 at K305 in in vitro tests; however, the physiological role of this modification has not yet been elucidated."

33302406

SETD7 affects TP53

2 2 | 61 32

SETD7 methylates TP53. 10 / 63

| 35 23

➶

sparser

"Thus, although Set9-mediated methylation of E2F1 destabilises the protein and impedes E2F1-mediated apoptosis, methylation of p53 by Set9 stabilises this transcription factor, which promotes apoptosis xref ."

23251702

➶

sparser

"P53 mono-methylation by SET7/9 is crucial for its stabilization and promoter occupancy ( xref )."

30881498

➶

reach

"Thus, human SET7/9 methylates p53 30 and TAF10; 31 and mammalian G9a methylates a range of nuclear protein targets CDYL1, WIZ, and ACINUS, 32 and is also capable of automethylation."

19422836

➶

reach

"If so, SET9 might be able to dimethylate p53, since water takes up the position of the second methyl group at the active site."

21625555

➶

reach

"SETD7 can also methylate p53 to increase its transcriptional activity."

23435229

➶

sparser

"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."

21963854

➶

sparser

"It is likely that SET7 methylates p53 and directly prevents p53 from being ubiquitylated as K372 is one of p53 ubiquitylation sites ( xref )."

21963854

➶

reach

"In HPV-non-infected normal cells (XREF_FIG), DNA damage induces SET7 mediated p53 methylation and stabilization, as well as p53 dependent recruitment of CARM1 and PRMT1 to p53-target gene promoters for transcriptional activation."

21963854

➶

reach

"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."

21963854

➶

reach

"P53 from cells stimulated with Adr was preferentially mono-methylated at K372 (compare lane 2 with lane 1) and prevented from degradation (compare lane 4 with lane 3), indicating that E6 preferentially degrades the endogenous p53 unmethylated by SET7."

21963854

SETD7 methylates TP53 on K372. 10 / 31

2 2 | 19 8

➶

reach

"Chuikov et al. showed that SET9 can specifically methylate p53 at K372 ."

30926778

➶

reach

"Furthermore, we have shown that methyltransferase Set7/9 that methylates p53 on K372 also interacts with Mdm2 thereby sequestering it away into a non functional complex thereby increasing acetylation and stabilization of the former [XREF_BIBR, XREF_BIBR]."

29290977

➶

reach

"P53 pre-methylated at lysine 372 (p53K372 mono-methylation) by SET7 protects p53 from E6 induced degradation."

21963854

➶

reach

"SETD7 methylates p53 at K372, enhancing p53 stability and its transcriptional activity."

30535125

➶

reach

"For example, Set7/9 methylates p53 on K372, which augments acetylation of K373 and K382 [XREF_BIBR]."

24298606

➶

reach

"However, some reports have pointed out that SET9 can dimethylate Lys372 of p53 (p53-K372) and Lys4 of histone H3 (H3-K4)."

21625555

➶

reach

"In 2004, they showed that Set7 and Set9 monomethylates p53 at lysine 372 (p53K372me1) [XREF_BIBR]."

24561874

➶

reach

"SMYD2 mono-methylates p53 on lysine K370 (p53K370me1), XREF_BIBR, XREF_BIBR while SET7 monomethylates p53 on lysine K372 (p53K372me1) XREF_BIBR in the regulatory domain."

23625014

➶

biopax:pid

No evidence text available

15525938

➶

sparser

"Recently, we discovered that lysine methylation of p53 at K372 by Set7/9 (also known as SET7 and Set9) is important for transcriptional activation and stabilization of p53."

17646389

SETD7 methylates TP53 on lysine. 8 / 8

| 7 1

➶

sparser

"C-terminal lysine residues of p53 are methylated in vivo at K370, K372, K373, and K382 by histone lysine methyl transferases, Smyd2, SET9, G9a/Glp, and Set8, respectively. xref – xref While K372 methylation by SET9 in human cells enhanced p53 transcriptional activities, the role of p53 methylation in the mouse by Set7/9 was controversial. xref – xref However, it should be pointed out that the results from mouse embryonic fibroblasts in the mouse study might be inappropriate to apply to human epithelial cells."

27270439

➶

reach

"Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines."

18581285

➶

reach

"Mechanism of product specificity of AdoMet methylation catalyzed by lysine methyltransferases : transcriptional factor p53 methylation by histone lysine methyltransferase SET7/9."

18260647

➶

reach

"For instance, lysine methylation of p53 by the SETD7 and the nuclear factor κB by the methyl transferase nuclear receptor-binding SET domain-containing protein 1 distinctly increase their ability to bind the promoter and activation of downstream genes [156, 158]."

30344952

➶

reach

"We provide the first genetic evidence demonstrating that lysine methylation of p53 by Set7/9 is important for p53 activation in vivo and suggest a mechanistic link between methylation and acetylation of p53 through Tip60."

18280244

➶

reach

"QPCR analysis also showed that Mll2 Gdf9 cKO oocytes overexpressed several apoptosis associated genes (XREF_TABLE), including p53 (transformation related protein 53; TRP53) and Setd7 (SET domain lysine methyltransferase 7, also know as Set7/9) (XREF_TABLE and XREF_SUPPLEMENTARY), which methylates p53 and prevents its degradation XREF_BIBR."

20808952

➶

reach

"In 2004, Chuikov et al. found that K372 of p53 is mono-methylated by Set7/9 lysine methyltransferase [49]."

17306845

➶

reach

"Originally defined as a critical layer of p53 regulation in human cell lines, p53 lysine methylation by Set7/9 (also called Setd7) was proposed to fulfill a similar function invivo in the mouse, promoting p53 acetylation, stabilization, and activation upon DNA damage (Kurash etal., 2008)."

21855806

PRMT5 affects TP53

| 49 40

PRMT5 methylates TP53. 10 / 62

| 27 33

➶

sparser

"These data support a mechanism wherein survival of D1T286A expressing cells is driven by and may require PRMT5-dependent methylation of p53."

25582697

➶

sparser

"Accumulated evidence also indicates that PMTs play their physiological and pathogenic roles through methylating nonhistone substrates. xref , xref Some recent advancements in this aspect include the identification of SET7/9 substrates: the tumor suppressors p53 and pRb, E2F1, HIV transactivator Tat, estrogen receptor α (ERα), PCAF, DNMT1, AKA6, CENPC1, MeCP2, MINT, PPARBP, ZDH8, Cullin1, IRF1, TAF7/10 subunits of TATA box-binding protein complex and RelA subunit of NF-κB; xref – xref G9a substrates reptin, mAM, WIZ, CDYL1, CSB, C/EBP and the tumor suppressor p53;(Pless, 2008 #63; Rathert, 2008 #9; Huang, 2010 #308; Lee, 2010 #309) SUV39H1 substrate HP1α; xref SETDB1 substrate ING2; xref and SMYD3 substrate VEGF receptor 1. xref These PMT-involved nonhistone methylation events modulate the functions of diverse cellular targets, such as histone-remodeling apparatus, tumor suppressors, transcription regulators, and hormone receptors. xref , xref Some nonhistone targets, similar to histones, can be modified by multiple PMTs (e.g. site-specific methylations of the tumor suppressor p53 by SET7/9, SET8, G9a, GLP1, SMYD2 and PRMT5), xref , xref , xref , xref , xref which may resemble the histone-code scenario for epigenetic regulation."

21866297

➶

reach

"Furthermore, PRMT5 monomethylates p53 within its oligomerization domain on a similar " GRG R / K " sequence to that found in histones, modestly influencing p53 tetramer formation and its target selection [XREF_BIBR]."

25662273

➶

reach

"PRMT5 interacts with and methylates p53 at Arg333/335/337 residues, affecting the promoter specificity of p53 associated with apoptosis or cell cycle arrest ."

34006904

➶

sparser

"For example, H4R3 can be methylated by PRMT1, PRMT5, PRMT6, and PRMT7; xref – xref TP53 can be methylated by PRMT3 and PRMT5; xref , xref and H3R2 can be methylated by PRMT5, PRMT6, and PRMT7. xref , xref To further understand the roles of each PRMT in cell biology, highly selective and cell-active inhibitors of each PRMT are needed."

33591753

➶

sparser

"Among others, PRMT5 methylates P53 thereby modifying its DNA-binding activity and suppressing the expression of proapoptotic and antiproliferative genes, which contributes to lymphomagenesis xref , xref ."

36167829

➶

sparser

"OXR1 was also shown to stimulate PRMT5-dependent methylation of p53, which results in cell cycle arrest."

33384581

➶

reach

"PRMT5 can also directly methylate p53, Rad9 (cell cycle checkpoint control protein), Fen1 (Flap endonuclease-1), and TDP (tyrosyl-DNA phosphodiesterase)(summarized in ), further corroborating the relevance of PRMT5 in DDR."

34052526

➶

reach

"XREF_BIBR, XREF_BIBR Some nonhistone targets, similar to histones, can be modified by multiple PMTs (e.g. site specific methylations of the tumor suppressor p53 by SET7/9, SET8, G9a, GLP1, SMYD2 and PRMT5), XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR which may resemble the histone-code scenario for epigenetic regulation."

21866297

➶

reach

"PRMT5 dependent methylation of p53 occurs within the p53 oligomerization domain suggesting a direct influence on p53 DNA binding and transcriptional output."

25582697

PRMT5 methylates TP53 on arginine. 10 / 14

| 13 1

➶

reach

"Arginine methylation of E2F1 and p53 by PRMT5 reportedly influences protein stability; therefore PRMT5 regulates cell cycle progression and cell death [14,22,23]."

25721668

➶

sparser

"In 2008, Jansson et al demonstrated that PRMT5 can methylate p53 at arginine residues 333, 335 and 337 to activate transcription of p21 and promote G 1 cell cycle arrest in response to DNA damaging agent etoposide ( xref )."

33854218

➶

reach

"6 A physical interaction of TTC5 with Protein Methyltransferase 5 (PRMT5), which arginine methylates TP53, has been reported, 7 as has a regulatory role for TTC5 in steroid hormone signaling where it acts as a cofactor for the glucocorticoid and estrogen receptors."

23559008

➶

reach

"In conclusion, the present study, using an innovative in vivo model integrating the stress responsive Gadd45beta-luciferase transgene and inducible oncogenes (LSL-K-ras G12D and Myc ER), uncovers two novel and significant findings : (i) normal HSPCs utilize arginine methylation of p53 by PRMT5 to orchestrate long lasting oncogenic response."

27507053

➶

reach

"In Fanca-/- and Fancc -/- mice, arginine methylation of p53 by PRMT5 was decreased in response to oncogenic stress [XREF_BIBR]."

29568320

➶

reach

"The authors showed that PRMT5 methylates p53 at selected arginine residues in p53 oligomerization domain."

19528079

➶

reach

"Thus, these studies defined a compromised oncogene induced arginine methylation of p53 by PRMT5 as one mechanism for the short lived oncogenic stress response in FA HSPCs."

27507053

➶

reach

"Because PRMT5 has been shown to mediate arginine methylation of p53 to regulate its function [XREF_BIBR, XREF_BIBR], we explored the effects of AMI-1 on p53 in nude mouse CRC xenograft model."

26078354

➶

reach

"Jansson et al. demonstrate that arginine methylation of p53 by PRMT5 regulates target gene specificity of p53 by altering promoter binding."

19450511

➶

reach

"A second centers on how arginine methylation of histones, E2F1 and p53 (as well as yet to be identified substrates) by PRMT5 is coordinated for neoplastic growth."

26425661

PRMT5 methylates TP53 on R335. 5 / 5

| 3 2

➶

reach

"PRMT5 induces arginine methylation of tumor suppressor p53 on the arginine 333,335 and 337 and affects the p53 target gene specificity, thereby escaping p53 surveillance and leading to tumorigenesis."

30713476

➶

reach

"The PRMT5 dependent methylation of p53 at residues R333, R335 and R337 represses the p53-DNA interaction."

32379587

➶

sparser

"Additionally, PRMT5 may directly methylate P53 on R333, R335 and R337, preventing its oligomerization with MDM2, which prevents TP53 binding to its target genes xref ."

36167829

➶

reach

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage (XREF_FIG)."

21975038

➶

sparser

"PRMT5 methylates p53 at R333, R335, and R337, resulting in changes in oligomerization, nuclear location, and DNA binding specificity. xref Moreover, DNA damage led to elevated p53 dimethylation."

34314149

PRMT5 methylates TP53 on R333. 5 / 5

| 3 2

➶

reach

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage (XREF_FIG)."

21975038

➶

sparser

"Additionally, PRMT5 may directly methylate P53 on R333, R335 and R337, preventing its oligomerization with MDM2, which prevents TP53 binding to its target genes xref ."

36167829

➶

sparser

"PRMT5 methylates p53 at R333, R335, and R337, resulting in changes in oligomerization, nuclear location, and DNA binding specificity. xref Moreover, DNA damage led to elevated p53 dimethylation."

34314149

➶

reach

"The PRMT5 dependent methylation of p53 at residues R333, R335 and R337 represses the p53-DNA interaction."

32379587

➶

reach

30713476

PRMT5 methylates TP53 on R337. 4 / 4

| 2 2

➶

sparser

"PRMT5 methylates p53 at R333, R335, and R337, resulting in changes in oligomerization, nuclear location, and DNA binding specificity. xref Moreover, DNA damage led to elevated p53 dimethylation."

34314149

➶

reach

"The PRMT5 dependent methylation of p53 at residues R333, R335 and R337 represses the p53-DNA interaction."

32379587

➶

sparser

"Additionally, PRMT5 may directly methylate P53 on R333, R335 and R337, preventing its oligomerization with MDM2, which prevents TP53 binding to its target genes xref ."

36167829

➶

reach

"In particular, PRMT5 interacts with and methylates p53 at R333, R335 and R337 upon DNA damage (XREF_FIG)."

21975038

Modified PRMT5 leads to the methylation of TP53 on arginine. 1 / 1

| 1

➶

reach

"As expected, ectopic PRMT5 expression increased arginine methylation of p53 in K-ras G12D -expressing WT and Fanca -/- leukemic cells."

27507053

SMYD2 affects TP53

1 1 | 45 37

SMYD2 methylates TP53. 10 / 58

| 32 25

➶

reach

"On the basis of the observation that p53 protein is methylated by SMYD2, which should lead to suppression of apoptosis, we were additionally interested in the effects of (S) -4 in combination with an apoptotic stimulus."

27075367

➶

sparser

"SMYD2 methylates p53 to prevent p53 from binding to its target gene promoters, and knockdown of SMYD2 enhances DNA damage-induced, p53-dependent apoptosis xref ."

29487338

➶

reach

21866297

➶

sparser

"Methylation of Lys370 p53 by Smyd2 reduces its binding efficiency to promoter genes, thereby repressing p53 transcriptional activity (Huang et al ., xref )."

31069954

➶

reach

"Smyd2 methylation of p53 reduced p53 occupancy at two target gene promoters : p21 and mdm2, and depletion of Smyd2 ramped up p53 mediated apoptosis in response to various types of DNA damage."

21826189

➶

reach

"Monomethylation of p53 by SMYD2 links SMYD2 to p53 mediated apoptosis and has been shown to contribute to tumorigenesis through inhibition of p53 transcriptional activity [17]."

24594358

➶

reach

"The methylation of p53 by SMYD2 has been observed in cells by several groups."

25825497

➶

sparser

"The methylation of p53 by SMYD2 can result in a repression of its function, which makes the SMYD2 a potential tumor suppressor. [32] Acyl-protein thioesterases (APT) are members of a protein group involved in depalmitoylation processes."

35563976

➶

reach

"These results suggested that the methylation of p53 or Rb by SMYD2 is not the principal driver of SMYD2 mediated cancer cell growth and that other SMYD2 substrates or a second genetic or epigenetic driver may be involved in the process."

28338320

➶

reach

"13 This antibody was then tested on recombinant p53 protein which had been in vitro methylated by SMYD2 in a Western blot."

27075367

SMYD2 methylates TP53 on K370. 10 / 24

1 1 | 11 11

➶

reach

"Smyd2 monomethylates p53 at lysine 370 [XREF_BIBR]."

24561874

➶

reach

"KMT3C, a member of the Smyd (SET and MYND domain) subfamily of SET domain containing proteins, mono-methylates p53 at K370."

18581285

➶

sparser

"It has been reported that the methyltransferase SMYD2 could methylate p53 at K370 in cancer cells xref ."

30926778

➶

reach

"P53 is methylated at K370 by Smyd2, K372 by Set 7/9, and K382 by Set8 (ref."

35487975

➶

sparser

"SMYD2 mono-methylates p53 on lysine K370 (p53K370me1), xref , xref while SET7 monomethylates p53 on lysine K372 (p53K372me1) xref in the regulatory domain."

23625014

➶

hprd

No evidence text available

17108971

➶

reach

"SMYD2 monomethylates Lys-370 of p53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53."

31106145

➶

sparser

"For instance, methylation of p53 on K370 by SMYD2 [ xref ] or on K382 by SETD8 [ xref ] results in transcriptional repression, whereas methylation at K372 by SET7/9 leads to activation of transcription [ xref ]."

21966347

➶

reach

"In this regard, it has been reported that SMYD2 can methylate p53 on Lys 370 and that this methylation leads to repression of its activity."

34143514

➶

sparser

"However, the methylation at p53-K372 by KMT5 prevents the methylation at p53-K370 by KMT3C ( xref )."

18581285

SMYD2 methylates TP53 on lysine. 2 / 2

| 1 1

➶

sparser

27270439

➶

reach

"Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines."

18581285

SMYD2 methylates TP53 on K372. 1 / 1

| 1

➶

reach

"P53 is methylated at K370 by Smyd2, K372 by Set 7/9, and K382 by Set8 (ref."

35487975

KMT5A affects TP53

1 | 36 20

KMT5A methylates TP53. 10 / 38

| 22 14

➶

reach

"SET8 contemporaneously monomethylates p53 to increase concentrations of the inactive p53K382me1 species, thus maintaining p53 quiescent (although poised) at a time when its tumor suppressing activities would derail healthy cell proliferation [XREF_BIBR]."

21826189

➶

reach

"SET8 reportedly methylates TP53 and regulates genomic stability."

22867998

➶

sparser

"SET8 methylates TP53 and regulates genome stability."

19789321

➶

reach

"SET8 methylates TP53 and regulates genome stability."

19789321

➶

sparser

"SETD6 targets the RelA subunit of the transcription factor NF-κB to regulate inflammation ( xref ); SETD7 has many cancer-associated substrates, including p53, the DNA methyltransferase DNMT1, the phosphatase PPP1R12A, which regulates cell cycle through Rb, and many others ( xref ); SETD8 methylates histone H4 as well as p53 and proliferating cell nuclear antigen (PCNA) ( xref ; xref ; xref ); SETMAR is involved in repairing DNA damage and methylates the splicing factor snRNP70 ( xref ; xref )."

27580749

➶

reach

"GST-p53 could not be in vitro methylated by Suv39H1, PR-Set7, or PRMT1."

17306845

➶

sparser

"Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines."

18581285

➶

sparser

"Importantly, these phenotypes were shown to be a consequence of SET8 methylation of p53, and not an indirect effect of H4K20 methylation by SET8 since H4K20me1 levels were not changed in the experimental system upon manipulation of SET8 levels, and expression effects on specific target genes were abolished upon p53 knockdown [ xref ]."

21826189

➶

sparser

"SET8 methylates TP53 and regulates genome stability."

20843204

➶

reach

"Since then, a number of other KMTs, including SET9 (KMT5), SMYD2 (KMT3C), and SET 8 (KMT5A), which methylate p53 at specific C-terminal lysines, together with the lysine specific demethylase KDM1 (LSD1) which mediates p53 demethylation, have also been identified [XREF_BIBR] (XREF_FIG)."

30050697

KMT5A methylates TP53 on K382. 10 / 18

1 | 12 5

➶

sparser

"The direct functional link between Setd8 and p63 remains elusive but recent studies showed that Setd8 methylates p53 at lysine 382 and thereby suppresses p53-mediated transcription in vitro ( xref )."

22117221

➶

reach

"We previously found that monomethylation of p53 at lysine 382 (p53K382me1) by the protein lysine methyltransferase (PKMT) SET8 and PR-Set 7 represses p53 transactivation of target genes."

20870725

➶

sparser

"The methylation of p53 on lysine 382 by SET8 is suggested to inhibit transcription of a subset of target genes, such as the CDK inhibitors p21 and PUMA."

23345616

➶

sparser

"As a methyltransferase, SET8 methylates lysine 382 of p53 to modulates p53 activity so as to change its transcriptional activity for downstream targets, furthermore, SET8 knockdown has been shown to upregulate cells’ sensitivity to cell death and cell cycle arrest following DNA damage by suppressing the biological function of p53 xref ."

27605386

➶

reach

"We find that SET8 specifically monomethylates p53 at lysine 382 (p53K382me1)."

17707234

➶

reach

"The p53 protein is also monomethylated at K382 (p53K382me1) by SET8."

23625014

➶

sparser

"Additionally, SETD8 can induce the mono-methylation of the tumor suppressor p53 at lysine 382 (p53K382me1), which attenuates its pro-apoptotic and growth arrest functions [ xref , xref ]."

| PMC

➶

biopax:pid

No evidence text available

17707234

➶

reach

"We chose to inactivate the methyl-transferase SET8, which has been shown to mediate the inhibitory methylation of p53 at K382."

20598361

➶

sparser

"Recently it has been shown that SET8 also methylates K382 in the p53 protein ."

22583696

KMT5A methylates TP53 on lysine. 3 / 3

| 2 1

➶

reach

"Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines."

18581285

➶

reach

"We previously found that monomethylation of p53 at lysine 382 (p53K382me1) by the protein lysine methyltransferase (PKMT) SET8 and PR-Set 7 represses p53 transactivation of target genes."

20870725

➶

sparser

27270439

PCMT1 affects TP53

| 14 12

PCMT1 methylates TP53. 10 / 20

| 5 12

➶

sparser

"To confirm that PIMT methylates p53 at isoaspartate residues 29 and 30, we synthesized peptides consisting of amino acids 22–40 of p53, in which asparagines 29 and 30 were replaced with isoaspartates (N29IsoD, N30IsoD and N29,30IsoD)."

22735455

➶

reach

"PIMT methylated the p53 peptide during a 30-min incubation period and the level of methylated peptide increased with increasing incubation time (XREF_FIG)."

22735455

➶

sparser

"We show that asparagine residues 29 and 30 of p53 are methylated by PIMT in vivo and in vitro ."

22735455

➶

reach

"Next, we determined whether PIMT methylates p53 under physiological conditions through nano-LC-ESI-MS/MS analysis of endogenous p53 purified from U2OS cells or ectopic expressed p53 purified from H1299 cells under conditions in which the PIMT catalyzed methylation of the isoaspartyl residues was stable enough for detection (XREF_FIG)."

22735455

➶

sparser

"Because PIMT interacted with p53 and its methylase activity was necessary for regulating p53, we examined whether PIMT directly methylates p53."

22735455

➶

sparser

"Because PIMT interacted with p53 and its methylase activity was necessary for regulating p53, we examined whether PIMT directly methylates p53."

22735455

➶

sparser

"PIMT methylated the p53 peptide during a 30-min incubation period and the level of methylated peptide increased with increasing incubation time ( xref )."

22735455

➶

reach

"Using an in vitro methylation assay, we found that PIMT methylated p53, whereas the PIMT G88A mutant did not (XREF_FIG and XREF_SUPPLEMENTARY)."

22735455

➶

sparser

22735455

➶

reach

"Because PIMT interacted with p53 and its methylase activity was necessary for regulating p53, we examined whether PIMT directly methylates p53."

22735455

PCMT1 methylates TP53 at position 29. 4 / 4

| 4

➶

reach

"PIMT methylates asparagine residues 29 and 30 of p53."

22735455

➶

reach

"We show that asparagine residues 29 and 30 of p53 are methylated by PIMT in vivo and in vitro."

22735455

➶

reach

"To confirm that PIMT methylates p53 at isoaspartate residues 29 and 30, we synthesized peptides consisting of amino acids 22-40 of p53, in which asparagines 29 and 30 were replaced with isoaspartates (N29IsoD, N30IsoD and N29,30 IsoD)."

22735455

➶

reach

"We also find that PIMT methylates p53 at isoaspartate residues 29 and 30, which is required to negatively regulate the p53 activity."

22735455

PCMT1 methylates TP53 on asparagine. 2 / 2

| 2

➶

reach

"PIMT methylates asparagine residues 29 and 30 of p53."

22735455

➶

reach

"We show that asparagine residues 29 and 30 of p53 are methylated by PIMT in vivo and in vitro."

22735455

PCMT1 methylates TP53 at position 30. 2 / 2

| 2

➶

reach

"PIMT methylates asparagine residues 29 and 30 of p53."

22735455

➶

reach

"We show that asparagine residues 29 and 30 of p53 are methylated by PIMT in vivo and in vitro."

22735455

PCMT1-G88A methylates TP53. 1 / 1

| 1

➶

reach

"The N terminus of p53 (amino acids 1-82) was methylated by PIMT, but not by the PIMT G88A mutant (XREF_FIG)."

22735455

EHMT1 affects TP53

| 11 10

EHMT1 methylates TP53 on K373. 10 / 13

| 7 6

➶

sparser

"Other study provides evidence that the G9a-GLP complex methylates p53 protein on Lys 373 residue and inactivates the growth suppression function of p53 in breast and lung cancer cells [ xref ]."

25027955

➶

reach

"In addition to methylating histone substrates, XREF_BIBR, XREF_BIBR, XREF_BIBR G9a and GLP dimethylate K373 of the tumor suppressor p53."

21780790

➶

reach

"Furthermore, GLP also methylates P53 directly on lysine 373 resulting in the inhibition of P53 activity (XREF_TABLE)."

24148750

➶

reach

"G9a and GLP methylate p53 at lysine 373."

27580749

➶

reach

"XREF_BIBR, XREF_BIBR - XREF_BIBR The di methylation of p53 K373 by G9a and GLP (also known as KMT1D or EHMT1), a closely related methyltransferase that shares 80% sequence identity with G9a in their respective SET domains and forms a heterodimer with G9a, results in the inactivation of p53, whose loss of function is implicated in over 50% of cancers."

21780790

➶

sparser

"Other study provides evidence that the G9a-GLP complex methylates p53 protein on Lys 373 residue and inactivates the growth suppression function of p53 in breast and lung cancer cells [ xref ]."

25027955

➶

reach

"Other study provides evidence that the G9a and GLP complex methylates p53 protein on Lys 373 residue and inactivates the growth suppression function of p53 in breast and lung cancer cells [XREF_BIBR]."

25027955

➶

sparser

"Furthermore, GLP also methylates P53 directly on lysine 373 resulting in the inhibition of P53 activity ( xref )."

24148750

➶

sparser

"G9a and GLP methylate p53 at lysine 373 ( xref )."

27580749

➶

sparser

"Recently, Huang and colleagues have reported that, in addition to acetylation and ubiquitylation, K373 of p53 can also be methylated by two homologous histone methyl- transferases, G9a and Glp [ xref ]."

24298606

EHMT1 methylates TP53. 6 / 6

| 2 4

➶

sparser

"G9a and Glp specifically methylate p53 at Lys(373), resulting mainly in dimethylation."

20118233

➶

reach

"For instance, SETD7, G9A, GLP and SETD8 methylate p53 (as well as other non histone substrates) 2."

31582846

➶

sparser

"For example, there is convincing evidence that G9a and GLP physiologically methylate LIG1, p53, WIZ, Reptin, ACINUS, CDYL1 and other substrates (see xref ), with LIG1 being a particularly high-affinity substrate xref ."

33469207

➶

sparser

33469207

➶

sparser

"For instance, G9a and GLP can methylate the tumor suppressor p53 [ xref ]."

21966348

➶

reach

21866297

EHMT1 methylates TP53 on lysine. 1 / 1

| 1

➶

reach

"G9a and Glp specifically methylate p53 at Lys (373), resulting mainly in dimethylation."

20118233

EHMT1 methylates TP53 at position 373. 1 / 1

| 1

➶

reach

"G9a and Glp specifically methylate p53 at Lys (373), resulting mainly in dimethylation."

20118233

TP53 affects TP53

1 | 10 5

TP53 methylates TP53. 8 / 8

| 4 4

➶

reach

"Moreover, bilateral partial ligation of the uterine arteries during pregnancy resulted in p53 hypomethylation and elevated expression of Bax and p53 as well as a reduction in Bcl-2 mRNA [XREF_BIBR]."

22778952

➶

sparser

"Oncogenic growth of such tumours is associated with reduced p53 activity caused by overexpression of one or more epigenetic regulators that post-translationally modify p53 protein and impair its tumour-suppressor functions, including Aurora A kinase that phosphorylates p53 (S212/S312) and methyltransferases that methylate p53 such as Smyd2 (K370), Glp/G9a (K373) and PR-Set7 (K382)."

32630614

➶

reach

"As p53 is (i) a key regulator of apoptosis and (ii) control the transcription of many apoptosis related-genes, silencing via methylation of p53 binding sites by the Dnmt3a and p53 complex may confer a signature participating in apoptosis resistance."

24709797

➶

sparser

"In the present study, we demonstrated that the age at which mice underwent 3-Gy whole-body irradiation leads to differences in TCR VF, percentage of apoptosis, expression of phospho-p53, ratio of the p53 allele and p53 methylation levels at 56 weeks of age (Table xref )."

23764457

➶

reach

"Because transcription factor occupancy can affect DNA methylation levels and DMR1 is within a p53 binding site at the DINO/CDKN1A locus, we examined whether TP53 status is associated with a differential methylation of p53 bound sites elsewhere in the genome (Younger et al., 2015)."

34192538

➶

reach

20808952

➶

sparser

"It was shown that a similar proportion of gliomas with and without P53 mutation present P53 promoter methylation ( xref )."

18349850

➶

sparser

"In the present study, we showed that the differences in expression of phospho-p53, the ratio of the p53 allele and p53 methylation levels at 56 weeks of age between mice that underwent 3-Gy whole-body irradiation at various ages (Table xref )."

23764457

TP53 methylates TP53 on lysine. 2 / 2

| 2

➶

reach

| 1

➶

reach

"Methylation specific PCR (MSP) showed that the amount of unmethylated p53 increased, indicating that the anthocyanins can down-regulate the methylation of p53."

24929515

SETDB1 affects TP53

| 10 6

SETDB1 methylates TP53. 9 / 9

| 6 3

➶

sparser

"Therefore, we decided to test whether SETDB1 could methylate p53."

26471002

➶

reach

"While endogenous SETDB1 can methylate either mutant or wild-type p53, mutant p53 appears to be methylated to a higher degree (XREF_SUPPLEMENTARY)."

26471002

➶

reach

"To ask whether SETDB1 can directly methylate full-length p53, we performed the in vitro methylation assay using the endogenous SETDB1 pull down complex and recombinant wild-type p53 protein."

26471002

➶

reach

"Therefore, we decided to test whether SETDB1 could methylate p53."

26471002

➶

reach

"In cancer cells that harbour the GOF, oncogenic TP53 mutations, such as R249S, the p53 protein is stabilized by interaction with and being methylated by SETDB1."

26471002

➶

reach

"Since wild-type p53 is only present in cells at a very low level, methylation of the wild-type tumour-suppressive p53 by SETDB1 may contribute very little to cell growth."

26471002

➶

reach

"We next tested methylation of endogenous p53 by endogenous SETDB1."

26471002

➶

sparser

"We next tested methylation of endogenous p53 by endogenous SETDB1."

26471002

➶

sparser

"Since wild-type p53 is only present in cells at a very low level, methylation of the wild-type tumour-suppressive p53 by SETDB1 may contribute very little to cell growth."

26471002

SETDB1 methylates TP53 on K370. 2 / 2

| 1 1

➶

sparser

"SETDB1 di-methylates p53K370 and subsequently regulates p53 stability."

26471002

➶

reach

"Although SETDB1 mediates histone H3K9 tri methylation as a histone methyltransferase, it remains to be determined whether SETDB1 can also tri-methylate p53 at K370."

26471002

SETDB1 methylates TP53 on lysine. 2 / 2

| 1 1

➶

reach

"SETDB1 complex di and methylates p53 at the 370 lysine residue."

26471002

➶

sparser

"SETDB1 complex di-methylates p53 at the 370 lysine residue."

26471002

SETDB1 methylates TP53 on K372. 2 / 2

| 1 1

➶

sparser

"Preliminary evidence suggested that SETDB1 might also methylate p53 at K372 and regulate its stability when K370 is mutated and is under overexpression conditions."

26471002

➶

reach

"Preliminary evidence suggested that SETDB1 might also methylate p53 at K372 and regulate its stability when K370 is mutated and is under overexpression conditions."

26471002

SETDB1 leads to the methylation of mutated TP53. 1 / 1

| 1

➶

reach

"(2) While SETDB1 methylates both wild-type and mutant p53, mutant p53 may have more chances to get K370 methylation in vivo because it associates more tightly with SETDB1 in cells as we have seen (XREF_SUPPLEMENTARY)."

26471002

EHMT2 affects TP53

| 12

EHMT2 methylates TP53. 6 / 8

| 6

➶

sparser

"For example, G9a methylates p53 and the myogenic regulator factor MyoD to inhibit their transactivation activity, whereas DNA ligase 1 methylated by G9a promotes the recruitment of UHRF1 and the maintenance of DNA methylation at DNA replication locus ( xref – xref )."

30854428

➶

sparser

"For instance, G9a and GLP can methylate the tumor suppressor p53 [ xref ]."

21966348

➶

sparser

33469207

➶

sparser

21866297

➶

sparser

"Moreover, as previously mentioned, G9a methylates the tumor suppressor p53, leading to its inactivation ( xref )."

26441991

➶

sparser

"G9a and Glp specifically methylate p53 at Lys(373), resulting mainly in dimethylation."

20118233

EHMT2 methylates TP53 on K373. 6 / 6

| 6

➶

sparser

"Interestingly, EHMT2 methylates lysine 373 in p53 ( xref )."

26763252

➶

sparser

"In addition, G9a methylates p53 at K373 and regulates apoptosis by preserving p53 in an inactive form ( xref )."

30535125

➶

sparser

24298606

➶

sparser

"G9a and GLP methylate p53 at lysine 373 ( xref )."

27580749

➶

sparser

"Other study provides evidence that the G9a-GLP complex methylates p53 protein on Lys 373 residue and inactivates the growth suppression function of p53 in breast and lung cancer cells [ xref ]."

25027955

➶

sparser

"G9a specifically methylates p53 at lysine 373, resulting in its inactivation xref ."

33468997

CXXC1 affects TP53

| 14

CXXC1 methylates TP53. 10 / 14

| 14

➶

sparser

"The incidence was 6.5% of p53 gene promoter CpG island methylation in 46 cases of laryngeal cancer, while methylation rate was 4.3% in adjacent tissues,no significant difference of p53 gene methylation was found in laryngeal cancer and counterparts adjacent tissues( P >0.05)."

29871161

➶

sparser

"We conclude that uteroplacental insufficiency alters p53 DNA CpG methylation, affects mRNA levels of key apoptosis-related proteins, increases renal apoptosis, and reduces glomeruli number in the IUGR kidney."

12869365

➶

sparser

"Uteroplacental insufficiency specifically decreased CpG methylation of the renal p53 BstU I site promoter without affecting the Hha I or the Aci I sites."

12869365

➶

sparser

"By contrast, the mean of p53 or RASSF1A promoter CpG sites methylation decreased in post-exposure DNA samples."

21878113

➶

sparser

"Before and after GT, we analyzed the levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA), p53 protein in serum, 5-methylcytosine (5-mC, global DNA methylation), and methylation in selected CpG sites of p53 gene."

32726118

➶

sparser

"The Ms-SNuPE assay provides a quantitative measure of the percent methylation at specific CpG sites in the promoter region of p53 gene."

11804744

➶

sparser

"As several TP53 CpG methylation sites are mutational hotspots in cancer (), an oligodeoxynucleotide corresponding to part of exon 8 was synthesized with 5MeC incorporated at two known sites of methylation in codons 273 and 282 ( xref )."

23840298

➶

sparser

"In the present study, we have determined the TP53 CpG methylation profile in the substituted segment of Hupki embryonic fibroblasts and compared it to the methylation profile of the same segment when present in normal human neonatal fibroblasts, using two independent assays, including the combined bisulfite-restriction analysis (COBRA) [ xref ], and sodium bisulfite genomic sequencing [ xref ]."

20945503

➶

sparser

"These data confirm that site‐specific changes of intragenic TP53 CpG methylation are extrinsically inducible, and suggest that human cancer progression is mediated in part by dysregulation of damage‐inducible intragenic CpG demethylation that alters TP53 P1/P2 isoform expression. © 2015 The Authors."

26676339

➶

sparser

"Pogribny et al. / Cancer Letters 115 (1997) 31-38 independent methylation of CpG sites in the p53 gene: impli- [33] Wu, J.J., Herman, J.G., Wilson, G., Lee, R.Y., Yen, R.W.C., cations for mutation[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

9097976

PRMT3 affects TP53

| 3 5

PRMT3 methylates TP53. 7 / 8

| 2 5

➶

sparser

33591753

➶

sparser

"Our study uncovered a novel aspect of the VHL-p53-ARF interaction, arginine methylation of p53 by VHL, ARF, and PRMT3."

21942715

➶

sparser

"We found that p53 was asymmetrically di-methylated by PRMT3 in the presence of VHL and ARF."

21942715

➶

reach

"For example, H4R3 can be methylated by PRMT1, PRMT5, PRMT6, and PRMT7; TP53 can be methylated by PRMT3 and PRMT5; and H3R2 can be methylated by PRMT5, PRMT6, and PRMT7."

33591753

➶

sparser

"ARF disrupts the E3 ligase complex containing VHL and instead enhances its interaction with the arginine methyltransferase PRMT3 which methylates p53 [ xref ]."

33406607

➶

sparser

"Further work is needed to elucidate the functional significance of p53 arginine methylation by PRMT3 in complex with VHL and ARF."

21942715

➶

reach

"ARF disrupts the E3 ligase complex containing VHL and instead enhances its interaction with the arginine methyltransferase PRMT3 which methylates p53 [XREF_BIBR]."

33406607

PRMT3 methylates TP53 on arginine. 1 / 1

| 1

➶

reach

"ARF and VHL30 promote p53 arginine methylation by PRMT3."

21942715

Methyltransferase activity affects TP53

| 8

Methyltransferase activity methylates TP53. 4 / 4

| 4

➶

sparser

"P53 can be methylated on lysines and arginines by several different methylase enzymes, which can either activate or repress its activity depending on which site is methylated and the number of methyl groups added ( xref )."

24124625

➶

sparser

"In contrast, methylation of p53 by methyltransferases at histidines, arginines, and lysines, suppresses transcriptional activity of p53 [ xref ]."

28208785

➶

sparser

"Several histone lysine methyltransferases methylate p53 at specific C-terminal lysines, preventing or inducing p53 interaction with its co-activators."

21483786

➶

sparser

"Our study identified PRMT3 as a second arginine methyltransferase that can methylate p53."

21942715

Methyltransferase activity methylates TP53 on K372. 3 / 3

| 3

➶

sparser

"In particular, methylation of p53 by SET7/9 methyltransferase on K372 results in p53 stabilization and increased p21 expression ( xref )."

28073943

➶

sparser

"It has recently been shown that p53 can be methylated at K372 by Set9 methyltransferase,[ xref ] and that the PHD finger of ING1/2 is required for p53 activity.[ xref , xref , xref ] Addition of the p53K372me3 or p53K372me1 peptides resulted in small chemical shift changes in the ING2 (and homologous ING1) PHD finger, however the binding was at least tenfold weaker than the interaction with unmodified H3."

19184981

➶

sparser

"Among these enzymes is Set9, a histone methyltransferase, which efficiently methylates p53 and E2F1 at Lys 372 and Lys 185 , respectively, with opposite consequences on their respective activities xref , xref ."

| 2

➶

reach

"Several histone lysine methyltransferases methylate p53 at specific C-terminal lysines, preventing or inducing p53 interaction with its co-activators."

21483786

➶

reach

"Indeed, histone lysine methyltransferases KMT5 (Set9), KMT3C (Smyd2), and KMT5A (Set8) methylate p53 at specific C-terminal lysines."

18581285

Histone leads to the methylation of TP53 on K372. 1 / 1

| 1

➶

reach

"Among these enzymes is Set9, a histone methyltransferase, which efficiently methylates p53 and E2F1 at Lys 372 and Lys 185, respectively, with opposite consequences on their respective activities XREF_BIBR, XREF_BIBR."

23251702

Histone methylates TP53 on K373. 1 / 1

| 1

➶

reach

24298606

Transferase affects TP53

| 1 5

Transferase methylates TP53 on lysine. 2 / 2

| 2

➶

sparser

"Methyl transferase enzymes (PRMT5—protein arginine methyltransferase 5, KMTs —lysine, K methyltransferases, SMYD2—SET And MYND domain containing 2, SET7/9, SET8—SET domain-containing proteins) can methylate several Lys and Arg residues of p53 during DNA damage response."

36138802

➶

sparser

27270439

Transferase methylates TP53 on K382. 2 / 2

| 1 1

➶

reach

"To test this idea, we used an siRNA to inhibit SET8, the monomethyl transferase that specifically methylates p53 at residue K382 (Shi et al., 2007)."

33961797

➶

sparser

"To test this idea, we used an siRNA to inhibit SET8, the monomethyl transferase that specifically methylates p53 at residue K382 ( xref )."

33961797

Transferase methylates TP53 on arginine. 1 / 1

| 1

➶

sparser

36138802

Transferase methylates TP53 on K373. 1 / 1

| 1

➶

sparser

24298606

SETD3 affects TP53

| 3 3

SETD3 methylates TP53. 6 / 6

| 3 3

➶

sparser

"In addition, In vitro methylation assay using recombinant purified proteins revealed that SETD3 does not methylate p53 (Fig. xref )."

30683849

➶

reach

"In addition, In vitro methylation assay using recombinant purified proteins revealed that SETD3 does not methylate p53."

30683849

➶

reach

"SETD3 does n't bind nor methylates p53 in vitro, but is required for p53 recruitment to its target genes."

30683849

➶

reach

"SETD3 does n't bind nor methylates p53 in vitro."

30683849

➶

sparser

"SETD3 doesn’t bind nor methylates p53 in vitro."

30683849

➶

sparser

"SETD3 doesn’t bind nor methylates p53 in vitro, but is required for p53 recruitment to its target genes."

30683849

KRAS affects TP53

| 6

KRAS methylates TP53. 6 / 6

| 6

➶

sparser

"Significantly, we demonstrated that disruption of the FA pathway compromised the oncogene K-ras G12D -induced arginine methylation of p53 mediated by the protein arginine methyltransferase 5 (PRMT5)."

27507053

➶

sparser

"However, K-ras-induced arginine methylation of p53 was peaked at 2 hours and almost completely abated after 8-hour induction with 4-OHT inFanca −/− Lin − cells (Figure xref ), reminiscent of the short-lived oncogenic response described above."

27507053

➶

sparser

"Mechanistic studies reveal that FA deficiency in HSPCs impairs oncogenic stress-induced G 1 cell-cycle checkpoint, resulting from a compromised K-ras G12D -induced arginine methylation of p53 mediated by the protein arginine methyltransferase 5 (PRMT5)."

27507053

➶

sparser

"There are several findings that highlight the significance of our study: 1) FA HSPCs displayed an aberrant short-lived response to oncogenic stress induced by activated K-ras or c-Myc; 2) Fanca deficiency compromises K-ras G12D -induced arginine methylation of p53 accompanied by downregulated PRMT5; 3) forced expression of PRMT5 inFanca −/− HSPCs prolonged oncogenic response and delayed leukemia development in irradiated recipient mice."

27507053

➶

sparser

"Remarkably, we showed that Fanca deficiency compromised K-ras G12D -induced arginine methylation of p53 accompanied by downregulated PRMT5 and that forced expression of PRMT5 inFanca −/− HSPCs prolonged oncogenic response and delayed leukemia development in irradiated recipient mice (Figure xref )."

27507053

➶

sparser

"Downregulation of Protein Arginine Methyltransferase 5 (PRMT5) led to compromised K-ras G12D -induced arginine methylation of p53 in FANCA deficient cells, thereby demonstrating an arginine methylation-dependent FA-p53 interaction, as forced expression of PRMT5 inFANCA −/− HSPCs prolonged oncogenic response and delayed leukemia development in irradiated recipient mice ( xref )."

29593731

IL6 affects TP53

| 4 1

IL6 leads to the methylation of TP53. 5 / 5

| 4 1

➶

sparser

"For example, IL-6 increased the methylation of p53 and p21 in A549 cancer cells by expression of DNMT1 ( xref )."

32478091

➶

reach

"One potential mechanism for this effect is through the activity of IL-6, which has been shown to support the aberrant methylation of the p53 promoter via up-regulation of DNMT1 gene expression."

20599773

➶

reach

"Moreover, previous studies also showed that increased DNMT1 expression mediated by IL-6 stimulation promotes hypermethylation of p21 and p53 in lung cancer cells [50], and SOCS3 in pancreatic cancer cells [51]."

32731382

➶

reach

"In multiple myeloma (MM) KAS 6/1 cells, IL-6 treatment leads to TP53 promoter methylation, resulting in decreased TP53 expression levels."

26073757

➶

reach

"The association between DNA methylation and cancer stage might be dependent on interleukin 6, a chronic inflammation marker that enhances the hypermethylation of tumor suppressor gene p53 families, but reduces the methylation of the epidermal growth factor receptor [XREF_BIBR]."

25815725

DNMT3B affects TP53

| 5

DNMT3B methylates TP53. 5 / 5

| 5

➶

reach

"In conclusion, our data strongly illuminates that ROS-PI3K and Akt pathway participates in the PM2.5-induced DNMT3B up-regulation, which leads to P53 promoter hypermethylation and down-regulation of P53 expression, a critical early event in epithelial cell carcinogenesis."

26942697

➶

reach

"On the other hand P53 also has been related with DNMT3b, since it has been identified that the hypermethylation of p53 promoter by DNMT3b causes a decrease of its expression level and promotes an increase of cell proliferation [XREF_BIBR]."

29290961

➶

reach

"MSPs of p53 and p21 were performed and revealed that silencing of DNMT3B decreased methylation of p53 and p21, respectively (XREF_FIG C and 5D)."

32382655

➶

reach

"These findings provide further evidence that DNMT3B mediates PM2.5-induced hypermethylation of P53 promoter."

26942697

➶

reach

"XREF_BIBR, XREF_BIBR Furthermore, note that silencing of DNMT3B decreased methylation of p53 and p21, respectively."

32382655

CDKN2A affects TP53

| 3 2

CDKN2A methylates TP53. 5 / 5

| 3 2

➶

sparser

"Our study uncovered a novel aspect of the VHL-p53-ARF interaction, arginine methylation of p53 by VHL, ARF, and PRMT3."

21942715

➶

reach

"20 In addition, the protein complex consisting of PRMT3, the von Hippel-Lindau (VHL) tumor suppressor protein, and ARF (alternative reading frame) methylates the tumor suppressor p53."

23445220

➶

sparser

"ARF and VHL30 promote p53 arginine methylation by PRMT3."

21942715

➶

reach

"Overexpression of p53 and hypermethylation of CDKN2A (P16INK-4a) have been reported in OSD ."

33179618

➶

reach

"There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene."

10461063

Selenium atom affects TP53

| 4

Selenium atom leads to the methylation of TP53. 4 / 4

| 4

➶

reach

"Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa."

21653573

➶

reach

"Furthermore, Se deficiency has been demonstrated to cause global hypomethylation and promoter methylation of the p16 and p53 tumor suppressor genes [XREF_BIBR]."

22022340

➶

reach

"For example, long-term selenium consumption increases exon specific DNA methylation of the p53 gene in rat liver and colon mucosa [XREF_BIBR]."

22928085

➶

reach

"The study whether selenium affects the methylation of the p53 gene was investigated, and it was found that supranutritional dose of selenium significantly increased the exon specific DNA methylation of the p53 gene (in exons 5-8) in liver and colon mucosa of rats compared with this in animals fed with the selenium deficient diet [XREF_BIBR]."

29065468

Arsenic atom affects TP53

2 | 2

Arsenic atom leads to the methylation of TP53. 4 / 4

2 | 2

➶

ctd

No evidence text available

21756780

➶

reach

"Knockdown of AS3MT by small interfering RNA reversed the arsenic induced RASSF1A promoter hypomethylation and TP53 hypermethylation (XREF_TABLE)."

24154821

➶

ctd

No evidence text available

16251483

➶

reach

"For example, it has been reported that arsenic could cause hypermethylation of the p53 gene."

27617186

PRMT1 affects TP53

| 3 1

PRMT1 methylates TP53. 4 / 4

| 3 1

➶

sparser

"Note that neither CARM1 nor PRMT1 methylated p53 (data not shown)."

21963854

➶

reach

"Note that neither CARM1 nor PRMT1 methylated p53 (data not shown)."

| 1

➶

reach

"MGMT methylation and type of KRAS and TP53 mutations."

25638164

DNMT1 affects TP53

| 4

DNMT1 methylates TP53. 4 / 4

| 4

➶

reach

"Here we show that in response to extensive hepatocyte damages, expression of dnmt1 is upregulated in BECs to methylate DNA at the p53 locus, which represses p53 transcription, and in turn, derepresses mTORC1 signaling to activate BEC dedifferentiation."

35351894

➶

reach

"Similarly, bisulfite sequencing analysis confirmed in HDFs that UVA irradiation caused demethylation of CpG in the p53 promoter region, while DNMT1 up-regulation could methylate CpG islands of p53, although the demethylation caused by UVA and DNMT1 induced methylation did not occurred at the same CpG islands (XREF_FIG)."

29466247

➶

reach

"We present, for the first time, direct evidence that DNMT1 modulates p53 methylation; furthermore, we precisely identify the sites of methylation within the p53promoter that are affected during UVA induced senescence."

29466247

➶

reach

"Bisulphite sequencing analysis indicated that DNMT1 and DNMT3beta did not cause p53 promoter hypermethylation."

27488808

Folic acid affects TP53

| 3

Folic acid leads to the methylation of TP53. 2 / 2

| 2

➶

reach

"These data indicate that secreted FOLR3 could induce p53 methylation by efficient folic acid uptake and affect the cell viability of SH-SY5Y cells.Endocytosis involves the process of transporting molecules into the cell by engulfing it with its membrane."

32581311

➶

reach

"In contrast, folic acid metabolizes homocysteine to methionine and induces p53 DNA methylation, supressing Hcy-induced toxicity ."

reach

"Monomethylation of p53 by SET and MYND domain-containing protein 2 (SMYD2) at K370, which was shown to repress p53-mediated transactivation, decreases the binding of p53 to the promoters of its target genes, such as p21."

32532965

➶

reach

30050697

Particulate Matter affects TP53

2 | 1

Particulate Matter methylates TP53. 3 / 3

2 | 1

➶

ctd

No evidence text available

29615218

➶

ctd

No evidence text available

26942697

➶

reach

"An in vitro study of human epithelial cells found that PM exposure resulted in hypomethylation of the TP53 promoter region and inhibition of TP53 expression."

34088750

PHF20 affects TP53

| 3

PHF20 methylates TP53. 3 / 3

| 3

➶

reach

"Dual recognition of doubly dimethylated p53 by PHF20 Tudor2."

22864287

➶

reach

"Furthermore, our findings are in line with previous studies that found that PHF20 could stabilize and activate p53 by promoting p53 methylation [XREF_BIBR], and that PHF20 inhibits p53 transcriptional activity via PKB mediated PHF20 phosphorylation [XREF_BIBR]."

29033691

➶

reach

"Our results are also consistent with a recent report that PHF20 leads to p53 stabilization and activation XREF_BIBR because PHF20 binding to methylated p53 protected it from SCF Fbxo22 -KDM4A mediated degradation (XREF_FIG)."

26868148

KITLG affects TP53

| 3

KITLG methylates TP53. 3 / 3

| 3

➶

reach

"These results indicate that SCF (Fbxo22)-KDM4A is an E3 ubiquitin ligase that targets methylated p53 and regulates key senescent processes."

26868148

➶

reach

"We demonstrate here that SCF (Fbxo22)-KDM4A is a senescence associated E3 ligase targeting methylated p53 for degradation."

26868148

➶

reach

"SCF (Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence."

26868148

HTN3 affects TP53

| 1 2

HTN3 leads to the methylation of TP53. 3 / 3

| 1 2

➶

sparser

"It is proposed that PB-induced de novo methylation of the p53 gene was not associated with DNMTs activity."

19227257

➶

reach

"We have demonstrated that PB increased the methylation of the p53 gene."

19227257

➶

sparser

"We have demonstrated that PB increased the methylation of the p53 gene."

19227257

CDK2AP2 affects TP53

"G9a and GLP methylate p53 at lysine 373 ( xref )."

27580749

Set9 affects TP53

| 2

1 | 1

Glyphosate leads to the methylation of TP53. 2 / 2

1 | 1

➶

reach

"These authors showed that high concentrations of glyphosate (from 84.54 to 1690 μg/ml) induce DNA lesions in peripheral blood mononuclear cells (PBMCs), decreased global 5mC percentage, and increased methylation of p53 promoter."

34093442

➶

ctd

No evidence text available

31751608

TP53BP1 affects TP53

| 2

TP53BP1 methylates TP53. 2 / 2

| 2

➶

reach

"For example, the 53BP1 tandem-Tudor domain binds to H4K20me3 and dimethylated p53 [XREF_BIBR, XREF_BIBR], and that of PHF20 has been shown to bind to lysine dimethylation of histones [XREF_BIBR] and p53 [XREF_BIBR]; in the latter case, PHF20 binding to p53 stabilizes p53 and promotes its activation during DNA damage response [XREF_BIBR]."

24035451

➶

| 2

Methyltransferases methylates TP53. 1 / 1

| 1

| 1

➶

reach

"Our data showed that p53 and JMJD3 directly interact after neural differentiation, and the presence or absence of JMJD3 demethylase function appears to differentially modulate the levels of p53 lysine methylation."

21483786

JMJD3 demethylase leads to the methylation of TP53. 1 / 1

| 1

➶

reach

"However, there could still be undiscovered methylation sites in the p53 protein that are targeted by JMJD3 demethylase activity."

24797517

HNMT affects TP53

| 2

HNMT methylates TP53. 2 / 2

| 2

➶

sparser

"In addition, only SET7 among these three HMTs methylates p53 under stress ( xref ; xref ; xref ; xref , and data not shown)."

21963854

➶

sparser

"It has been shown that HMTs, such as KMT7, KMT3C, KMT5A and EHMT2, can methylate p53 at distinct sites xref xref xref xref ."

26471002

GCG affects TP53

| 1 1

GCG methylates TP53. 2 / 2

| 1 1

➶

reach

"GLP1 methylates its canonical substrate histone H3 as well as diverse biologically relevant non-histone substrates such as DNMT3A (Chang et al., 2011), p53 (Huang et al., 2010), C/EBP-β (Pless et al., 2008), Reptin (Lee et al., 2010), and MyoD (Ling et al., 2012) without consensus substrate-recognizing sequences."

34370893

➶

sparser

21866297