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TP53 is methylated on K372. 58 / 58
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sparser
"We also show that reduced PRMT5 expression leads to cyclin D1 transcriptional repression via loss of TP53K372 methylation, which results in decreased BCL3 expression and enhanced recruitment of NF-κB p52-HDAC1 repressor complexes to the cyclin D1 promoter."

sparser
"A dynamic sequential relationship exists between p53K372 methylation and p53 acetylation, with DNA damage increasing SET9-mediated p53K372me1 levels and this in turn promoting acetylation."

sparser
"KDM3A was found to impede the methylation of p53K372, which subsequently restricted the activity of p53 and the expression of p21."

sparser
"In contrast, SET7/9-catalyzed p53K372 methylation adopts an extremely early S N 2 TS with the short 2.0 Å C–S distance and the long 2.3 Å C–N distance (the S–N distance around 4.3 Å, xref )."

sparser
"The latter may be due to JMJD1A-mediated reduction of lysine 372 methylation on TP53, a methylation mark known to increase TP53 stability and nuclear localization."

sparser
"Several studies have demonstrated that Set7/9-mediated methylation of p53-K372 facilitates acetylation of the adjacent lysine residues (K373 and K382) in p53 [ xref , xref ]."

sparser
"In order to improve our understanding of the Smyd2 catalytic cycle, here we carried out μ‐second MD simulations of the following systems (see Fig.  xref ): Smyd2 in complex with AdoMet cofactor (Model‐A); Smyd2‐AdoMet‐p53 peptide (unmethylated) complex (Model‐B); Smyd2‐AdoHcy‐p53 peptide (methylated at Lys370) complex (Model‐C); and Smyd2‐AdoMet in complex with the p53 peptide methylated at Lys372 (Model‐D)."

sparser
"Set7 mediated methylation of Lys372 in P53 increases its stability, resulting in the induction of P53 target genes ( xref )."

sparser
"Previous report suggested that mono methylation of p53 at K372 enhances the transcriptional activity by stabilizing the chromatin bound p53. xref Therefore, we quantified the p53 occupancy on p21 promoter by chromatin immunoprecipitation (ChIP) assay."

sparser
"For example, methylation of p53 K372 depends on the addition of an acetyl moiety on neighboring lysine residues (Kurash et al , xref )."

sparser
"This is due to an inhibitory effect of p53-K372 methylation on the interaction between KMT3C and p53."

sparser
"However, only KO cells have elevated levels of Lysine 372 methylated p53."

sparser
"Interestingly, adriamycin–induced accumulation of acetylated p53 on the p21 promoter can be further stimulated by methylation at K372 of p53 by Set-7/9, a lysine-specific histone methyltransferase [ xref ]."

sparser
"We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2 and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120."

sparser
"Furthermore, methylated p53-K372 is transcriptionally hyperactive to induce target genes, including cyclin-dependent kinase inhibitor p21, pro-apoptotic BAX, and MDM2."

sparser
"In contrast, SETD7-mediated p53 methylation at K372 has been shown to enhance p53 activity xref ."

sparser
"E6 also inhibits SET7, which, in addition to catalyzing H3K4 monomethylation, methylates non-histone proteins, including p53 and downregulates p53K372 mono-methylation, thereby reducing p53 stability [ xref ]."

sparser
"P53 methylation at Lys372 has notable effects on the accessibility of Lys370 to the cofactor."

sparser
"Remarkably, SET7/9 adopts two structurally distinct TS---a nearly symmetric S N 2 and an extremely early S N 2---for H3K4 and p53K372 methylation, respectively."

sparser
"Given the lower methylation of p53 at K372 associated with a lower activity of p53 in KD over KO cells, it is possible that KD mice are less capable to eliminate accumulated myeloid cells than KO mice."

sparser
"The methylation of p53 at the Lys372 residue induces acetylation at adjacent lysine residues, resulting in activation of p53 transcriptional activity ( xref )."

sparser
"Furthermore, the level of K370 methylation was attenuated concomitant with the increase of K372 methylation in p53 after genotoxic stress [ xref ]."

sparser
"Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53 protein stability."

sparser
"Set9 promotes cell death via methylation of p53 at lysine-372, which stabilizes the protein during DNA damage ( Chuikov et al., 2004; Ivanov et al., 2007; Kurash et al., 2008 )."

sparser
"Further, the PCA and corresponding projections along the principal eigenvectors (Fig.  xref C) reveal a restricted conformational basin for Lys372‐methylated p53, which correlates with other structural characteristics mentioned above."

sparser
"SET domain containing lysine methyltransferase 7/9 (SET7/9) is one of the proteins that regulate p53 through PTMs, which mono-methylates p53 at lysine 372 (K372) that results in its stabilization and activation ( xref , xref )."

sparser
"In HPV E6-expressing cells ( xref ), E6 attenuates stress-induced p53 function at least through the following two distinct pathways: (1) E6 downregulates p53 protein stability depending on E6AP ( xref , xref ) or by inhibiting SET7-mediated p53 methylation at K372 ( xref )."

sparser
"For example, previous research has demonstrated that SET7 specifically methylated p53 at lysine 372, and methylated p53-K372 localized to the nucleus xref ."

sparser
"Indeed, methylation at p53-K372 has no effect on the total ubiquitination of p53 and therefore is unlikely to directly prevent p53 degradation ( xref ; xref )."

sparser
"Interestingly, in a recent study, Ivanov et al. found that the methylation at p53-K372 facilitates the acetylation at p53-K373/K382 by KAT3B. However, the pre-acetylation at p53-K373/K382 prevents the methylation at p53-K372 by KMT5."

sparser
"These findings suggest that p53 methylation at K372 precedes p53 acetylation at adjacent lysines."

sparser
"On the other hand, SET7-mediated methylation of p53 at K372 enhances the association of p53 with promoters by blocking SMYD2-mediated methylation of K370, which promotes activation of the target genes xref ."

sparser
"In a human osteosarcoma cell line, Set7/9 was shown to methylate p53 on K372, promoting its stabilization and the activation of its downstream targets ( Chuikov et al., 2004 )."

sparser
"In contrast to p53-K372 methylation, SMYD2-catalyzed K370 monomethylation (K370me1) of p53 represses gene-activating function of p53 by reducing chromatin-associated p53, suggesting that K370 monomethylation is a repressive mark for p53 activity [ xref ]."

sparser
"We and others have reported that aberrant methylation of oncoproteins and tumor suppressor proteins plays important roles in development/progression processes of a variety of human cancers. xref , xref Our previous studies indicated that methylation on non‐histone proteins affected subcellular localization, stability, and other modifications of several oncogenic proteins; xref , xref , xref , xref for example, methylation of heat shock protein 70 by SETD1A promotes its nuclear translocation and interaction with Aurora kinase B. xref We have also shown that demethylation of lysine residues in MYPT1, a retinoblastoma 1 phosphorylation regulator, by lysine‐specific histone demethylase 1 destabilizes the MYPT1 protein and promotes cell cycle progression in cancer cells. xref Other groups showed that methylation of lysine 372 of p53 by SETD7 increases protein stability and enhances p53 activity, xref whereas monomethylation of lysine 370 by SMYD2 represses p53 function. xref Furthermore, the activities of several protein kinases were shown to be under the control of lysine methylation; methylation of vascular endothelial growth factor receptor 1 xref and AKT1 xref by SMYD3 leads to enhancement of autophosphorylation."

sparser
"In addition, p53-K372 methylation results in stabilization of the chromatin-associated p53 fraction [ xref ]."

sparser
"Given that SET7/9 catalyzes H3K4 and p53K372 methylation with comparable k cat (1.1–1.2 min −1 ), xref the activation energy of the two TS from the SAM-SET7/9-substrate Michaelis complexes are expected to be similar."

sparser
"Intriguingly, we found that 17β−E 2 treatment significantly attenuated methylation of p53 at Lysine 372 following global cerebral ischemia, which may contribute to decreasing stability and activity of p53 and to the overall neuroprotective effect of 17β−E 2 ( data not shown )."

sparser
"Therefore, the present study determined the protein expression of methylated p53 K372 (p53 K372-Me ) in the presence of resveratrol or DMSO ( xref )."

sparser
"In tumor cell lines, Set7/9 (also called Setd7 or KMT7) was shown to methylate K372 of human p53, thereby contributing to its stabilization and activation ( Chuikov et al., 2004 )."

sparser
"Finally, Gfi1 also decreases the pro-apoptotic effects of p53 in lymphoblastic leukemia by binding to the regulatory regions of pro-apoptotic genes, such as BAX , Pmaip1 ( NOXA ), and Bbc3 ( PUMA ); blocking p53 binding; and decreasing methylation of p53-K372 [ xref ]."

sparser
"However, the methylation at p53-K372 by KMT5 prevents the methylation at p53-K370 by KMT3C ( xref )."

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

sparser
"For example, methylation of the tumor suppressor p53 at K372 by the methyltransferase Set9 activates its transcriptional function, while the Smyd2-mediated methylation of p53 at K372 has an opposite role ( xref , xref )."

sparser
"KMT3C has no effect on the total level of p53, the level of acetylated p53-K382, phosphorylated p53-S15, or methylated p53-K372."

sparser
"In light of these surprising results, we sought to recapitulate earlier findings and investigated the impact of loss of Set7/9 on the monomethylation of p53 on K369, as previously assessed through an [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"For example, KMT7-mediated p53K372 methylation prevents p53K370 methylation mediated by SMYD2 (ref. xref ) but facilitates p53K373/K382 acetylation xref ."

sparser
"Finally, it has been demonstrated that p53 can be methylated at Lysine 372 , which leads to enhanced stability and activity of p53 xref ."

sparser
"Furthermore, the level of methylated p53-K372 rapidly increased in response to DNA damage, whereas the levels of Set7/9 by itself remained largely unaffected."

sparser
"SET7/9 catalyzes mono-methylation of p53 at K372."

sparser
"Indeed, SET7-mediated p53K372 methylation primes p53 acetylation on several sites in the C-terminus ( xref ; xref ), and p53 acetylation increases p53 stability by blocking the ubiquitination sites of p53 ( xref )."

sparser
"Notably, methylation of p53 at K372 leads to increased stability of chromatin-bound p53 and to the activation of p53 target genes, whereas demethylation of K372 has an inhibitory effect on p53 ( xref )."

sparser
"Gfi1 exerts this function by (i) co-occupying p53 target genes such as Bax , Pmaip1 and Bbc3 , (ii) binding to p53-bound transcriptional complexes and (iii) limiting the methylation of p53 at K372 thereby restricting the activity of p53 and the activation of p53 target genes."

sparser
"The authors proposed that p53-K372 methylation induced it subsequent acetylation by p300/CBP on K373 and K382."

sparser
"Further, methylation of p53 at C-terminal residue K372 contributes to the p21 gene activation by increasing the affinity between p53 and the p21 promoter ( xref )."

sparser
"The function of Gfi1 to limit p53-K372 methylation (p53-K369 in murine cells)( xref ) appears to be dependent on its ability to bind SNAG-dependent cofactors such as LSD1."

sparser
"By comparison, methylation at K372 of p53 promotes its acetylation at K373 and K382 in response to various stresses ( xref ), but inhibits K370 methylation by Smyd2 (ref. xref )."