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Statements

TP53 is methylated on K370. 61 / 61
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"It rather appears to create a binding site for additional modifying enzymes since cells lacking methylation of lysine 372 are also deficient in acetylation of lysine 320, lysine 373, and lysine 382 as well as methylation of lysine 370 of p53."
19929178
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"For example, LSD1 removes the methylation at residue K370 of p53 to inhibit its role in promoting apoptosis ( Huang et al., 2007 ) and demethylates the RB regulator MYPT1 to promote cell-cycle progres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25773598
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"Mechanistically, SMYD2 prompt cell migration, increase the tumor sphere and block apoptosis, which is dependent on the methylation of p53 K370 ."
31106145
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"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
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"Previous reports showed that SMYD2 overexpression promotes the methylation of Lys370 in p53 and inhibits p53-mediated transcriptional regulation, leading to cancer occurrence ( xref )."
34335697
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"The results showed that JMJD2a and LSD1 overexpression successfully abrogated CK2 downregulation-induced senescence and that CK2 knockdown inhibited JMJD2a and LSD1 mRNA translation, thereby increasing p53 K370 methylation."
35000672
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"In contrast, more fluctuations are observed for the unmethylated peptide (Model‐B) and the p53 methylated at Lys370 (Model‐C)."
31069954
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"The p53 peptide methylated at Lys370 exhibits higher mobility compared to the unmethylated or methylated at Lys372 one."
31069954
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"By methylating p53 at K370, Smyd2 may also impact the activity of cell cycle regulators."
23047121
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"Recent studies revealed that p53K370, K372 and K382 can also be methylated, indicating cross-regulation between acetylation, methylation and ubiquitynation."
21371315
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"Furthermore, mono-methylation at K372 was shown to inhibit the methylation of p53 on K370, using another methyl-K370-specific antibody ( xref )."
30907951
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"LSD1 can specifically demethylate the di-methylation of p53 at the lysine 370 site, making p53 a mono-methylation state xref ."
38572094
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"Collectively, the mutual binding of LSD1 and p53 leads to the conversion from di-methylation to mono-methylation at the lysine 370 site of p53, which in turn enhances the enzymatic activity of LSD1."
38572094
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"In addition, SMYD2 is reported to methylate the K370 site of p53 repressing its antitumor effect ( xref ), whereas SMYD2 induces RB1 methylation at lysine 810 in some cancers that promotes cell cycle progression of these malignant cells ( xref )."
38758030
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"Interestingly, p53-K370 methylation can be reversed."
26305020
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"It is proposed that SMYD2 suppressed p53-dependent apoptosis by methylating the p53 transcription factor at lysine 370 in cardiomyocytes, as shown in xref [ xref ]."
36838987
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"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
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"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
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"In addition, mono-methylation of P53 at Lys 370 has been shown to repress P53-mediated transcriptional regulation and apoptosis induction in H1299 cells [ xref ]."
21615965
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"On a molecular level, SMYD2 promotes cell motility, expands the tumor sphere, and inhibits apoptosis, which is reliant on p53K370 methylation."
37513898
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"This protein forms a complex with p53 and catalyses p53 K370 di-methylation."
32441252
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"A cocrystal structure reveals the origin of enhanced potency, and effective suppression of p53K370 methylation is observed in a lung carcinoma (A549) cell line."
26101576
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"The lysine K373 of p53 interacts directly with the side-chain of SMYD2Y344 through van der Waals interactions, whereas its ε-amine of p53K373 forms hydrogen bonds OH groups of Y370 and Y374. xref Thus, G9A-mediated dimethylation of p53, p53K373me2, could hypothetically increase interactions with SMYD2 aromatic cage, as seen with the cation-π interactions-mediated increased affinity between ING4 PHD and H3K4 me3 , xref and lead to methylation of p53 at K370."
23625014
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"First, SMYD2 was reported to methylate p53 on lysine 370, repressing its activity [ xref ]."
27655694
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"As further proof of the existence of the link, we focused on p53 di-methylated on lysine 370."
38731890
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"Methylation of p53 on lysine 370 can be reversed by the lysine demethylase LSD1 [ 47 • ], with some preference to removing the dimethylation of this residue."
19179064
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"It is reported that LLY-507 may also show improved inhibition of TP53-K370 mono-methylation in cells, but the primary data are not yet published and the phenotypes this compound elicits in disease-rel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25578037
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"LLY-507 Inhibits SMYD2-mediated Methylation of p53 Lys 370 in Cells."
25825497
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"For instance, the methylation of the tumor suppressor p53 at K372 by the methyltransferase SET9 activates its transcriptional function, while the SMYD2-mediated methylation of p53 at K370 exerts the opposite effect ( xref , xref )."
38113258
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"P53 Methylation at K370, K373, and K382 suppresses p53 transcriptional activity, whereas methylation at K372 facilitates its activity."
33462212
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"Post‐translational modifications (PTMs) enrich the functional diversity of proteins and affect many biological processes in both eukaryotes and prokaryotes. [ xref , xref ] Site‐specific methylation of non‐histone lysine residues is a prevalent PTM and has been regarded as a novel regulatory mechanism to control protein function, primarily affecting protein stability. [ xref , xref ] SETDB1, also known as ESET or KMT1E, is a member of the SET domain‐containing histone methyltransferases, and can catalyze H3K9 di‐ and tri‐methylation to repress gene transcription. [ xref ] Recently, many studies have highlighted the role of SETDB1‐mediated methylation in non‐histone proteins. [ xref , xref , xref ] For instance, SETDB1 catalyzes p53K370 di‐methylation and promotes its ubiquitination‐mediated degradation, leading to tumor growth. [ xref ] Our previous study reveals that SETDB1‐mediated Akt K64 methylation plays a critical role in tumorigenesis. [ xref ] "
37541664
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"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
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"LSD1 removes methylation at K370 of p53 which regulates the association of p53 with p53-binding protein 1 and so modulates p53 activity xref ."
27481483
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"Recently LSD1 was shown to repress p53-mediated transcriptional activation by removing methylation at K370 of p53 ."
18501190
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"The methylation of p53 at K370 has been shown to repress p53-mediated apoptosis in response to DNA damage as well as regulate the expression of downstream target genes such as p21, a cyclin-dependent [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29382574
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"SMYD2 catalyzes the methylation of the p53 protein at lysine 370, which represses p53-dependent transcription ( xref )."
27334938
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"Importantly, overexpression of mutant variants of GFI1 that cannot interact with LSD1, namely GFI1 P2A and GFI1 ΔSNAG, did not lead to a decrease in p53-K370 di-methylation (Fig.  xref )."
31004086
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"Additionally, SETDB1 has been found to methylate non-histones, such as tri-methylating AKT at K64 and K140 (AKT K64me3 and AKT K140me3 ), and di-methylating P53 at K370 (P53 K370me2 ) [ xref – xref ]."
38057834
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"However, recent biochemical and cellular studies indicate that mammalian SMYD2 protein is an H3K36-specific HMT xref , and surprisingly, that it is able to methylate p53 on the lysine 370 and thereby inhibit the tumor suppressing function of p53 xref ."
18231586
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"Here we report that SMYD2 prefers to methylate p53 Lys-370 over histone substrates in vitro."
21880715
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"In addition, the histone demethylase LSD1 specifically removes mono- or di-methylation at K370 of p53 to repress p53-mediated transcriptional activation [ xref ]."
29755654
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"LSDl can remove methylation of the tumor suppressor protein p53 K370, inhibit p53 activity, and inhibit p53 target gene expression[ xref - xref ]."
31435463
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"The published study by Huang et al. suggests that K370-methylation of p53 reduces DNA-binding efficiency, and SMYD2-mediated methylation at K370 shifts the equilibrium towards dissociation of p53 from DNA xref ."
30926778
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"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
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"Methylated TP53 (TP53 K370me2) is significantly more active in inducing apoptosis than unmethylated TP53. xref We therefore investigated whether IMG-7289 treatment affects TP53K370 methylation as well as total TP53 expression."
31723778
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"In this study, we disclose LLY-507, a small molecule inhibitor of SMYD2 with the following biochemical, biophysical, and cellular properties: 1) has low nanomolar IC 50 in SMYD2 biochemical assays; 2) has 100-fold selectivity for SMYD2 over 24 other protein or DNA methyltransferases including related family members SMYD3, SUVH420H1, and SUV420H2; 3) inactive (>20 μ m ) against 454 kinases, 35 G protein-coupled receptors, 14 nuclear hormone receptors, and three cytochrome P450 enzymes; 4) binds to substrate channel of SMYD2 based upon a high (1.6-Å) resolution crystal structure; 5) has submicromolar cell-based potency as demonstrated by its ability to inhibit the mono-methylation of Lys 370 of p53 in several different cell systems; and 6) has antiproliferative activity in tumor types in which SMYD2 is amplified and/or overexpressed."
25825497
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"Furthermore, in response to DNA damage, the level of methylated p53-K370 associated with the p21 promoter is decreased."
18581285
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"This suggests that methylation of p53 at K370, in contrast to methylation at K372, has a repressive effect on p53 activity."
18581285
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"Methylation at residue K370 on p53 represses its antitumor ability by inhibiting p53-mediated cancer cell apoptosis, while methylation at K382 represses its transcriptional activity [ xref , xref ]."
39127633
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"Furthermore, we reported that p53 is a target of SMYD2 and that SMYD2 methylates p53 at K370 to reduce its protein stability."
34015314
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"Similarly, the mechanism underlying the repressive effect of methylated p53-K370 needs further investigation."
18581285
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"Intriguingly, methylation of p53 at K370 was greatly increased in Fbxo22-depleted RPE cells in the presence of MG132, whereas acetylation at this site was not ( xref )."
26868148
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"To address whether methylation of p53K370 is mediated by SETDB1 methyltransferase activity, we transfected HCT116 p53 null cells with p53 together with wild-type or catalytically dead SEDTB1."
26471002
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"We thus asked whether di-methylation of p53 at K370 would be involved in the regulation of p53 stability."
26471002
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"This inhibitor clearly suppressed p53K370 methylation mediated by SMYD2 in lung carcinoma A549 cells."
26751963
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"Methylation of K370 of p53 impairs its ability to bind to the promoters of target genes ( xref ; xref )."
25321194
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"We took advantage of LLY-507 to determine the time frame at which p53 Lys 370 methylation is affected in response to inhibition of SMYD2 catalytic function."
25825497
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"For example, KMT7-mediated p53K372 methylation prevents p53K370 methylation mediated by SMYD2 (ref. xref ) but facilitates p53K373/K382 acetylation xref ."
26471002
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"Together, our data revealed a novel function of SETDB1 to regulate HCC cell growth through p53K370 di-methylation."
26471002
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"On the other hand, SMYD2-mediated methylation of p53 at K370 shifts the equilibrium towards dissociation of p53 from DNA and downregulates expression of p21 and MDM2 , thereby inhibiting cell apoptosis xref ."
30926778
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"Huang et al. showed that methylation at K372 inhibits the interaction of p53 with Smyd2 and subsequent K370 methylation [ xref ] and p53 methylation at K370 influences p53 acetylation [ xref ]."
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