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SETD7 methylates TP53. 99 / 104
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"This idea is supported by the findings that the histone methyltransferase SET9 methylates the tumor suppressor protein p53 [42] , demonstrating that SET domain proteins have broader substrate specific[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18375123
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"Methylation of p53 by the KMT7(SET7/9) methyltransferase enzyme on Lys372 in the C-terminal region of the protein following DNA damage results in p53 stabilization and trans-activation of p53 target genes like p21 [ xref ]."
18923809
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"Although SET9, SmyD2 and SET8 could directly methylate p53 at its C-terminus, other SET domain-containing proteins could not methylate p53 at least in vitro , including Suv39h1, Suv4-20h1 and hDOT1L [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18585004
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"The most reasonable explanation for the disparity of in-vitro and in-vivo studies is that methylation of p53 by SET7/9 has no functional effect on p53 function."
35069908
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"P53 mono-methylation by SET7/9 is crucial for its stabilization and promoter occupancy ( xref )."
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"Pathway integration is another, given that SET7/9 methylates both p53 [ 3 ] and pRB [ 4 ], suggesting that SET7/9 integrates different tumor suppressor pathways.It is well established that some protei[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region."
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"SETD7 methylates crucial molecules in numerous significant signalling pathways, including STAT3 [50], p53 [51], HIF-1α [52] and PARP1 [53]."
38670954
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"This idea is supported by the findings that the histone methyltransferase SET9 methylates the tumor suppressor protein p53 [42] , demonstrating that SET domain proteins have broader substrate specific[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18375123
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"Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo."
19929178
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"Another study shows that methylation of p53 by Set7/9 is required for Tip60 binding to p53 and subsequent acetylation of p53."
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"We found that Set7/9, but not its catalytically inactive mutant, methylated the wild-type Sam68 protein along with p53 ( Fig. 2 B)."
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"Methylation of p53 by SET7 (KMT7) was the first KMT mediated methylation of a nonhistone protein reported [XREF_BIBR]."
30050697
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"Kurash et al. reported that the methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53."
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"They provided the first genetic evidence demonstrating that lysine methylation of p53 by Set7/9 is important for p53 activation in vivo and suggested a mechanistic link between methylation and acetyla[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Set7/9 methylates the p53 protein, which leads to p53 stabilization via inactivation of SIRT1 by its methylation."
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"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."
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"Set7/9 methylates the p53 protein, which leads to p53 stabilization via inactivation of SIRT1 by its methylation.Another article by Evers et al. sheds light on metabolic changes in lung cancer describes the epithelial-mesenchymal transition in relationship with extracellular ATP (eATP) and TGF-beta."
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"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 ."
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"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)."
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"In addition, methylation of p53 by Set9 in vivo increases its stability and regulates the expression of p53 dependent genes."
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"Furthermore, the in vivo function of p53 methylation by Set7 remains debatable ( xref , xref , xref )."
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"For instance, SETD7, G9A, GLP and SETD8 methylate p53 (as well as other non histone substrates) 2."
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"As expected, SET7 methylated p53 and histone H3, but not nucleosomes ( Figure 1 A) ( Chuikov et al., 2004 )."
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"Of note, SET7/9 and SMYD2 methylation on p53, for example, are mutually inhibitory and the crosstalk between them and additional posttranslational modifications can lead to the distinct functional outcomes under different biological conditions [ xref , xref , xref ]."
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"SET7/9 methylated p53 as expected ( xref , left panels) and also JMJD2D ( xref , right panels)."
38045004
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"It is important to note that p53 methylation by SETD7, specifically at K372, prevents the addition of other PTMs that inhibit p53 activity [ xref – xref ]."
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"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."
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"The methyltransferase SETD7 methylates several of the proteins embedded within these networks : p53 [142], retinoblastoma tumour suppressor protein (pRb) [143], myosin phosphatase target subunit 1 (MYPT1) [144], and transcription factor E2F1 [145]."
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"For example, methylation of p53 by mammalian SET9 has been shown to cause the retention of p53 in the nucleus and increase the stability of an otherwise highly unstable protein and, consequently, regu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"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."
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"SETD7 can also methylate p53 to increase its transcriptional activity."
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"Methylation of p53 by Set7/9 has also been shown to mediate p53 acetylation by the acetyltransferase Tip60, which appears to bind preferentially to p53 methylated at lysine 372 [63] ."
19217357
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"Methylation of p53 by Set7/9 has also been shown to mediate p53 acetylation by the acetyltransferase Tip60, which appears to bind preferentially to p53 methylated at lysine 372 [63] ."
19217357
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"Among those, methylation of p53 by SET7/9 (Chuikov et al , xref ) was initially reported to promote the pro‐apoptotic activity of the transcription factor in stimulating its acetylation by p300/CBP (Ivanov et al , xref )."
24714364
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"Methylation of p53 by SET7 (KMT7) was the first KMT-mediated methylation of a nonhistone protein reported [ xref ]."
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"Among those, methylation of p53 by SET7/9 (Chuikov etal, 2004) was initially reported to promote the pro apoptotic activity of the transcription factor in stimulating its acetylation by p300 and CBP (Ivanov etal, 2007)."
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"Methylation of p53 by Set7/9 is damage-responsive and appears to precede acetylation and stabilization of p53 [62] ."
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"The interaction between Set7/9 and Sirt1 plays a more critical role in enhancing p53 activity than does p53 methylation mediated by Set7/9 ( Liu et al., 2011 )."
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"Indeed, we and others showed that Set7/9 is able to directly methylate the p53 protein, which leads to p53 stabilization and nuclear translocation and enhances the expression of p53 target genes (11, 59)."
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"Methylation of p53 by Set7/9 is damage-responsive and appears to precede acetylation and stabilization of p53 [62] ."
19217357
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"Mechanistically, SETD7 deficiency reduced p53 mono-methylation and blocked FBXO45 transcription, thereby inhibiting the protein degradation of GPX4 and subsequent lipid peroxidation as well as oxidative stress."
40275362
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"Although SET9, SmyD2 and SET8 could directly methylate p53 at its C-terminus, other SET domain-containing proteins could not methylate p53 at least in vitro , including Suv39h1, Suv4-20h1 and hDOT1L [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18585004
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"SET7/9 methylated p53 as expected ( Figure 1B , left panels) and also JMJD2D ( Figure 1B , right panels)."
38045004
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"To understand the molecular mechanism of Set7/9-mediated regulation of p53 function in vivo, we first confirmed that mouse p53 is methylated by Set7/9 in vitro (lysine 369, Figures 1 A and 1B) and the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18280244
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"Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo."
19929178
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"Indeed, since the discovery of p53 methylation by SET7/9, an array of non histone proteins were shown to be targeted by SET7/9, including nuclear receptors, chromatin associated transcriptional factors and co-factors, and chromatin modifying enzymes, among others."
26902152
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"In vitro methylation experiment demonstrated that SETD7 was responsible for the mono-methylation of p53 ( p53) (Fig. 7B)."
40275362
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"Kurash et al. reported that the methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53."
25911240
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"Mechanistically, SETD7 medicates methylation of p53 to promote the transcription of FBXO45, which results in ubiquitination and degradation of GPX4 and subsequent severe dysfunction."
40275362
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"For example, methylation of p53 by mammalian SET9 has been shown to cause the retention of p53 in the nucleus and increase the stability of an otherwise highly unstable protein and, consequently, regu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17512990
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"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
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"Thus, human SET7/9 methylates p53 and TAF10; and mammalian G9a methylates a range of nuclear protein targets CDYL1, WIZ, and ACINUS, and is also capable of automethylation."
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"20 With their experimental KIEs as computational constraints, we revealed that SET7/9 methylates the H3 and p53 peptides via nearly symmetrical and extremely early S N 2 TS, respectively."
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"SETD7 can also methylate p53 to increase its transcriptional activity ( xref )."
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"Another study shows that methylation of p53 by Set7/9 is required for Tip60 binding to p53 and subsequent acetylation of p53."
31282934
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"The HKMTs SET9, SMYD2, G9a and SET8 can methylate four of the six lysine sites at the C-terminus of the p53 protein to modulate its function ( xref )."
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"Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region."
15525938
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"It was identified that histone-lysine N-methyltransferase SET9 could mono-methylate p53 at K372 (p53-K372me1) and sustain its transcriptional activity [ 40 ]."
32569864
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"For example, methylation of SOX2, p53, HIF-1α, and β-catenin by SET7 is involved in regulating their stability, subcellular localization, and/or activities ( Chuikov et al., 2004; Fang et al., 2014; L[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In order to understand how p53 can be dimethylated by SET9, we measured the radius of the channel that surrounds p53-K372, first on the basis of the crystal structure of SET9, and we show that the channel is not suitable for water movement."
21625555
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"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."
21963854
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"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
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"It is likely that SET7 methylates p53 and directly prevents p53 from being ubiquitylated as K372 is one of p53 ubiquitylation sites ( xref )."
21963854
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"SET7/9 methylate p53 is a transcription factor that regulates p21 expression, thereby enhancing p21 gene expression."
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"Alternatively, p53 methylation by SET7 might indirectly influence p53 protein stability by facilitating p53 acetylation."
21963854
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"These mechanisms likely explain how p53 methylation by SET7 resists E6-dependent p53 degradation through E6AP/ubiquitin ( xref , xref )."
21963854
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"Thus, Set7/9-dependent methylation of p53 is currently considered a central regulatory event in the modulation of its transactivation potential."
21855805
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"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
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"For instance, SET9-dependent p53 methylation positively affects its stability [ 34 ] and SET8-dependent p53 methylation at lysine 382 (p53K382me1) significantly inhibits p53-mediated transcriptional a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Methylation of p53, by SET7/9, increased the binding of p53 to the promoter region of the p21 gene, resulting in the increased acetylation of histone H4 and the subsequent transcriptional activation and cell cycle arrest (Figure 2)."
37446210
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"Methylation of p53, by SET7/9, increased the binding of p53 to the promoter region of the p21 gene, resulting in the increased acetylation of histone H4 and the subsequent transcriptional activation and cell cycle arrest ( xref )."
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"Methylation of p53 by Set7 stabilizes p53 ( Chuikov et al., 2004 ), whereas methylation of DNMT1 by Set7 stimulates DNMT1 proteasomal degradation ( Estève et al., 2009; Wang et al., 2009; Estève et al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Of note, several lysine residues near the site where SET7/9 methylates p53 can also be acetylated by CBP/p300 [20]."
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"Interestingly, the tumor suppressor p53 was recently shown to be methylated in established cancer cell lines by two histone methyltransferases, Set7/9 and Smyd2 ( Chuikov et al., 2004; Huang et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In vitro binding experiments further show that Tip60 can preferentially bind to methylated p53 even after removing Set7/9 from the mix, indicating that Set7/9 does not act as an adaptor protein for th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In particular, methylation of p53 by SET7/9 methyltransferase on K372 results in p53 stabilization and increased p21 expression."
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"Of note, several lysine residues near the site where SET7/9 methylates p53 can also be acetylated by CBP/p300 [ xref ]."
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"Methylation of p53 by Set7 stabilizes p53 (Chuikov et al., 2004), whereas methylation of DNMT1 by Set7 stimulates DNMT1 proteasomal degradation (Esteve et al., 2009; Wang et al., 2009; Esteve et al., [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"SET7/9 also methylates p53 tumor suppressor, and recognizes a conserved K/R-S/T/A motif preceding the lysine substrate, with a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target."
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"For example, methylation of SOX2, p53, HIF-1α, and β-catenin by SET7 is involved in regulating their stability, subcellular localization, and/or activities ( Chuikov et al., 2004; Fang et al., 2014; L[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30008322
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"P53 mono-methylation by SET7/9 is crucial for its stabilization and promoter occupancy."
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"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_BIBR."
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"In addition to showing that SETD7 directly methylates TP53, the researchers showed an alternative way in which the transactivation capacity of TP53 can be enhanced during the DNA damage response."
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"In this paper, the authors demonstrated that upon DNA damage, SET9 mono-methylation of p53 at lysine 372 (p53K372me1; see XREF_FIG) in the nucleus results in stabilization of chromatin bound p53."
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"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."
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"We continued to investigate whether p53 pre-methylated by SET7 resists E6 mediated degradation."
21963854
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"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."
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"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
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"Interestingly, the amount of p53 methylated by endogenous Set7/9 increased after cells were treated with a DNA damaging agent."
17306845
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"Given that p53 pre-methylated by SET7 resists E6 triggered degradation (XREF_FIG), inhibition of SET7 by E6 might prime E6 mediated p53 degradation."
21963854
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"In addition, only SET7 among these three HMTs methylates p53 under stress."
21963854
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"It is likely that SET7 methylates p53 and directly prevents p53 from being ubiquitylated as K372 is one of p53 ubiquitylation sites."
21963854
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"Alternatively, p53 methylation by SET7 might indirectly influence p53 protein stability by facilitating p53 acetylation."
21963854
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"Although TRP53 was not identified in our screening, methylation of TRP53 by SETD7 (Set7/9) has been reported in cancer settings xref ."
35115604
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"These mechanisms likely explain how p53 methylation by SET7 resists E6 dependent p53 degradation through E6AP and ubiquitin."
21963854
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"Chuikov et al. showed that SET9 can specifically methylate p53 at K372 xref ."
30926778
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"Thus, Set7/9-dependent methylation of p53 is currently considered a central regulatory event in the modulation of its transactivation potential."
21855805
sparser
"Indeed, since the discovery of p53 methylation by SET7/9, an array of non-histone proteins were shown to be targeted by SET7/9, including nuclear receptors, chromatin-associated transcriptional factors and co-factors, and chromatin-modifying enzymes, among others."
26902152