IndraLab

Statements

TP53 is methylated on K382. 37 / 37
| 37
sparser
"The p53–L3MBTL1 interaction is driven in vivo by SET8-mediated methylation of p53 at lysine 382 [ xref ]."
21826189
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
"Indeed, the methylation of p53 at K382 prevents p53 binding to p21 and PUMA promoters."
18581285
sparser
"Based on these data, we conclude that SET8 methylates p53 exclusively at K382."
17707234
sparser
"To confirm the extent of methylation on p53K382 catalyzed by SET8, peptides bearing amino acids 367–389 of p53 were in vitro methylated by SET8 and analyzed by mass spectrometry."
17707234
sparser
"Other important non-histone KMT5A targets include: Tumor protein P53 (p53), which is methylated at K382 (p53K382me1) [ xref ] and Numb, which is methylated on K158 and K163 [ xref ]."
30832413
sparser
"Methylation of lysine-382 in p53 may block acetylation of that residue and prevent activation of p53 [ xref ]."
23747316
sparser
"We also tested the ability of αp53K382me1 to recognize p53 methylated at K382 in the context of the full-length p53 protein."
17707234
sparser
"For example, the MBT domains of L3MBTL1 were found to directly interact with methylated p53K382, RbK860, and H4K20 [ xref , xref – xref ]."
24525102
sparser
"Moreover, in other ischemic diseases, Smyd-2 inhibits p53-dependent cardiomyocyte death by methylating lysine 382 on p53, thereby reducing its transcriptional activity [ xref ]."
39682718
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
"Given that SETD8 is directly implicated in the Lys382 methylation of p53 and consequent modulation of its p21 ‐inducing and antiapoptotic activity (Shi et al ., xref ), it is plausible that SETD8's action in the senescence pathway is exerted via a p53‐dependent manner."
28514051
sparser
"Our ChIP results instead showed a biased distribution of SETD8 and H4K20me1 in the p21 gene body, particularly in the PC3 cells (Fig.  xref ). (ii) The biological contexts in which SETD8 was dissected were different—while the earlier report elucidated functional relevance of the SETD8‐mediated methylation at Lys382 of p53 in apoptosis (Shi et al ., xref ), our work focused on the connection of SETD8 to p21 expression during cellular senescence."
28514051
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
"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
"SET8 mediated mono-methylation of p53 at K382 promotes the methyl specific interaction of p53 with the MBT domains of L3MBTL1 protein which mediates the repression of p53 target genes xref xref ."
26391684
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 find that SET8-mediated methylation of p53 at K382 represses highly responsive p53 target genes to attenuate p53 proapoptotic and cell-cycle arrest functions."
17707234
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
"SET8 modulates p53 expression by methylating p53 at lysine 382."
24146953
sparser
"If SET8 repression of p53 target genes occurred via H4K20 methylation rather than p53K382 methylation, then the transactivation activity of WT and mutant p53K382R proteins should both be equally affec[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17707234
sparser
"Furthermore, methylation of p53 at lysine-382 prevents its interaction with co-activator 53BP1 and induces apoptosis [28] ."
21266164
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
"Recent studies revealed that p53K370, K372 and K382 can also be methylated, indicating cross-regulation between acetylation, methylation and ubiquitynation."
21371315
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
"P53 Methylation at K370, K373, and K382 suppresses p53 transcriptional activity, whereas methylation at K372 facilitates its activity."
33462212
sparser
"However, we do observe a SET8-dependent upregulation of the DNA repair gene GADD45, indicating that p53K382 methylation might have more complex regulatory roles than simply contributing to on/off func[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17707234
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
sparser
"Indeed, KMT5A is well-known to methylate p53 at K382 to reduce p53 activation [ xref ], and the down-regulation of KMT5A in response to DNA damage has been shown to result in the conversion of this mono-methylation state into a di/tri- methylation state on K382 to increase p53 stability [ xref , xref ]."
37509260
sparser
"Interestingly, the level of methylated p53-K382 is decreased upon treatment with the radiomimetic drug neocarzinostatin, which correlates with an increase in acetylation at the same residue ( xref )."
18581285
sparser
"Besides H4K20me2, L3MBTL1 was also reported to recognize methylation on p53K382 ( West et al., 2010 )."
33894155
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
"For example, SETD8 protein performs mono-methylation of p53 (p53K382me1) on lysine 382 which inhibits p53-dependent transcriptional activation in tumor cells [ xref ]."
37308924
sparser
"It is tempting to speculate that under no or low cellular stresses, the presence of methylated p53-K382 may favor p53-mediated DNA repair vs. apoptosis (cell survival vs. cell death)."
18581285
sparser
"SET8-mediated methylation of p53 at K382 promotes the interaction between L3MBTL1 and p53 in p53 target promoters ( xref ."
31282934
sparser
"SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53 K382me1 ), resulting in the inhibition of its pro-apoptotic and growth-arresting functions."
40165182
sparser
"In particular, it is the sole known mono-methyltransferase that mono-methylates p53 on lysine 382 (p53 K382me1 ), which results in the inhibition of p53 pro-apoptotic and growth-arresting functions [ xref ]."
40165182