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SETD7 methylates TP53. 58 / 63
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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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"P53 mono-methylation by SET7/9 is crucial for its stabilization and promoter occupancy ( xref )."
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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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"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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"SETD7 can also methylate p53 to increase its transcriptional activity."
23435229
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"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."
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 ( xref )."
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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."
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"These data indicate that E6 only degrades p53, which is not previously methylated by SET7."
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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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"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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"P53 mono-methylation by SET7/9 is crucial for its stabilization and promoter occupancy."
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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 ."
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"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."
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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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"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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"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."
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"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 in vivo in the mouse, promoting p53 acetylation, stabilization, and activation upon DNA damage (Kurash et al., 2008)."
21855806
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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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"Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region."
15525938
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"SETD7 can also methylate p53 to increase its transcriptional activity ( 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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"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
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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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"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."
23251702
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"Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region."
15525938
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"Importantly, we find that 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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"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
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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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"Importantly, we find that methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53."
18280244
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"Furthermore, the in vivo function of p53 methylation by Set7 remains debatable ( xref , xref , xref )."
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"Alternatively, p53 methylation by SET7 might indirectly influence p53 protein stability by facilitating p53 acetylation."
21963854
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"Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo."
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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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"We continued to investigate whether p53 pre-methylated by SET7 resists E6 mediated degradation."
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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 ]."
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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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"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."
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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."
21826189
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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."
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"These mechanisms likely explain how p53 methylation by SET7 resists E6 dependent p53 degradation through E6AP and ubiquitin."
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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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"Chuikov et al. showed that SET9 can specifically methylate p53 at K372 xref ."
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"In particular, Set7/9 (KMT7)-mediated monomethylation of human p53 at lysine 372 (p53K372me1) was suggested to be essential for p53 activation in human cell lines."
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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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"In addition, only SET7 among these three HMTs methylates p53 under stress."
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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"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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"In addition, methylation of p53 by Set9 in vivo increases its stability and regulates the expression of p53 dependent genes."
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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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"For instance, SETD7, G9A, GLP and SETD8 methylate p53 (as well as other non histone substrates) 2."
31582846
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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]"
25042802
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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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"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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"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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"Methylation of p53 by SET7 (KMT7) was the first KMT mediated methylation of a nonhistone protein reported [XREF_BIBR]."
30050697
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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
sparser
"These mechanisms likely explain how p53 methylation by SET7 resists E6-dependent p53 degradation through E6AP/ubiquitin ( xref , xref )."
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