IndraLab

Statements

TP53 is methylated on K370. 45 / 45
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"This inhibitor clearly suppressed p53K370 methylation mediated by SMYD2 in lung carcinoma A549 cells."
26751963
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"Similarly, the mechanism underlying the repressive effect of methylated p53-K370 needs further investigation."
18581285
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"In addition, the histone demethylase LSD1 specifically removes mono- or di-methylation at K370 of p53 to repress p53-mediated transcriptional activation [ xref ]."
29755654
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"As shown in xref D , significant reductions in p53 Lys 370 methylation occurred by 18 h following LLY-507 treatment of SMYD2-overexpressing KYSE-150 cells."
25825497
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"Furthermore, in response to DNA damage, the level of methylated p53-K370 associated with the p21 promoter is decreased."
18581285
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"Although the site of Smyd2-mediated methylation on the p53 protein at lysine 370 has already been discovered, the authors have shown that the methylation status of p53 at K370 does not affect binding of p53 to its target promoters."
33824417
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"Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase, which has been shown to repress p53-mediated apoptosis in response to various types of DNA damage by methylation of the transcription factor p53 at lysine 370 [ xref , xref ]."
25014164
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"The p53 peptide methylated at Lys370 exhibits higher mobility compared to the unmethylated or methylated at Lys372 one."
31069954
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"Recently LSD1 was shown to repress p53-mediated transcriptional activation by removing methylation at K370 of p53 ."
18501190
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"SMYD2 catalyzes the methylation of the p53 protein at lysine 370, which represses p53-dependent transcription ( xref )."
27334938
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"In addition, mono-methylation of P53 at Lys 370 has been shown to repress P53-mediated transcriptional regulation and apoptosis induction in H1299 cells [ xref ]."
21615965
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"Huang et al. showed that methylation at K372 inhibits the interaction of p53 with Smyd2 and subsequent K370 methylation [ xref ] and p53 methylation at K370 influences p53 acetylation [ xref ]."
24561874
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"This protein forms a complex with p53 and catalyses p53 K370 di-methylation."
32441252
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"We took advantage of LLY-507 to determine the time frame at which p53 Lys 370 methylation is affected in response to inhibition of SMYD2 catalytic function."
25825497
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"Here we report that SMYD2 prefers to methylate p53 Lys-370 over histone substrates in vitro."
21880715
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"To address whether methylation of p53K370 is mediated by SETDB1 methyltransferase activity, we transfected HCT116 p53 null cells with p53 together with wild-type or catalytically dead SEDTB1."
26471002
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"For example, LSD1 removes the methylation at residue K370 of p53 to inhibit its role in promoting apoptosis ( Huang et al., 2007 ) and demethylates the RB regulator MYPT1 to promote cell-cycle progres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25773598
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"SMYD2 was later shown to regulate tumor suppression via mono-methylation at p53K370 or RB1K860 and K810 ( xref – xref ) by induction of apoptosis or cell cycle arrest, respectively."
32115575
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"On the other hand, SMYD2-mediated methylation of p53 at K370 shifts the equilibrium towards dissociation of p53 from DNA and downregulates expression of p21 and MDM2 , thereby inhibiting cell apoptosis xref ."
30926778
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"Previous reports showed that SMYD2 overexpression promotes the methylation of Lys370 in p53 and inhibits p53-mediated transcriptional regulation, leading to cancer occurrence ( xref )."
34335697
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"Recent studies revealed that p53K370, K372 and K382 can also be methylated, indicating cross-regulation between acetylation, methylation and ubiquitynation."
21371315
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"Interestingly, p53-K370 methylation can be reversed."
26305020
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"LLY-507 Inhibits SMYD2-mediated Methylation of p53 Lys 370 in Cells."
25825497
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"First, SMYD2 was reported to methylate p53 on lysine 370, repressing its activity [ xref ]."
27655694
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"P53 Methylation at K370, K373, and K382 suppresses p53 transcriptional activity, whereas methylation at K372 facilitates its activity."
33462212
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"For example, KMT7-mediated p53K372 methylation prevents p53K370 methylation mediated by SMYD2 (ref. xref ) but facilitates p53K373/K382 acetylation xref ."
26471002
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"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
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"By methylating p53 at K370, Smyd2 may also impact the activity of cell cycle regulators."
23047121
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"Mechanistically, SMYD2 prompt cell migration, increase the tumor sphere and block apoptosis, which is dependent on the methylation of p53 K370 ."
31106145
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"We thus asked whether di-methylation of p53 at K370 would be involved in the regulation of p53 stability."
26471002
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"However, recent biochemical and cellular studies indicate that mammalian SMYD2 protein is an H3K36-specific HMT xref , and surprisingly, that it is able to methylate p53 on the lysine 370 and thereby inhibit the tumor suppressing function of p53 xref ."
18231586
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"A cocrystal structure reveals the origin of enhanced potency, and effective suppression of p53K370 methylation is observed in a lung carcinoma (A549) cell line."
26101576
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"Furthermore, mono-methylation at K372 was shown to inhibit the methylation of p53 on K370, using another methyl-K370-specific antibody ( xref )."
30907951
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"Intriguingly, methylation of p53 at K370 was greatly increased in Fbxo22-depleted RPE cells in the presence of MG132, whereas acetylation at this site was not ( xref )."
26868148
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"In contrast, more fluctuations are observed for the unmethylated peptide (Model‐B) and the p53 methylated at Lys370 (Model‐C)."
31069954
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"The lysine K373 of p53 interacts directly with the side-chain of SMYD2Y344 through van der Waals interactions, whereas its ε-amine of p53K373 forms hydrogen bonds OH groups of Y370 and Y374. xref Thus, G9A-mediated dimethylation of p53, p53K373me2, could hypothetically increase interactions with SMYD2 aromatic cage, as seen with the cation-π interactions-mediated increased affinity between ING4 PHD and H3K4 me3 , xref and lead to methylation of p53 at K370."
23625014
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"Together, our data revealed a novel function of SETDB1 to regulate HCC cell growth through p53K370 di-methylation."
26471002
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"LSD1 removes methylation at K370 of p53 which regulates the association of p53 with p53-binding protein 1 and so modulates p53 activity xref ."
27481483
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"Importantly, overexpression of mutant variants of GFI1 that cannot interact with LSD1, namely GFI1 P2A and GFI1 ΔSNAG, did not lead to a decrease in p53-K370 di-methylation (Fig.  xref )."
31004086
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"In this study, we disclose LLY-507, a small molecule inhibitor of SMYD2 with the following biochemical, biophysical, and cellular properties: 1) has low nanomolar IC 50 in SMYD2 biochemical assays; 2) has 100-fold selectivity for SMYD2 over 24 other protein or DNA methyltransferases including related family members SMYD3, SUVH420H1, and SUV420H2; 3) inactive (>20 μ m ) against 454 kinases, 35 G protein-coupled receptors, 14 nuclear hormone receptors, and three cytochrome P450 enzymes; 4) binds to substrate channel of SMYD2 based upon a high (1.6-Å) resolution crystal structure; 5) has submicromolar cell-based potency as demonstrated by its ability to inhibit the mono-methylation of Lys 370 of p53 in several different cell systems; and 6) has antiproliferative activity in tumor types in which SMYD2 is amplified and/or overexpressed."
25825497
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"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
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"Methylation of K370 of p53 impairs its ability to bind to the promoters of target genes ( xref ; xref )."
25321194
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"This suggests that methylation of p53 at K370, in contrast to methylation at K372, has a repressive effect on p53 activity."
18581285
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"Methylated TP53 (TP53 K370me2) is significantly more active in inducing apoptosis than unmethylated TP53. xref We therefore investigated whether IMG-7289 treatment affects TP53K370 methylation as well as total TP53 expression."
31723778
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"The published study by Huang et al. suggests that K370-methylation of p53 reduces DNA-binding efficiency, and SMYD2-mediated methylation at K370 shifts the equilibrium towards dissociation of p53 from DNA xref ."
30926778