IndraLab

Statements


TP53 is methylated on K382. 24 / 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."

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 )."

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."

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 ]."

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

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

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."

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 )."

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

sparser
"Methylation of lysine-382 in p53 may block acetylation of that residue and prevent activation of p53 [ xref ]."

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 ."

sparser
"For example, the MBT domains of L3MBTL1 were found to directly interact with methylated p53K382, RbK860, and H4K20 [ xref , xref – xref ]."

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."

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."

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

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)."

sparser
"The p53–L3MBTL1 interaction is driven in vivo by SET8-mediated methylation of p53 at lysine 382 [ xref ]."

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
"SET8 modulates p53 expression by methylating p53 at lysine 382."

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 ]."

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 )."

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."

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."