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SMYD2 methylates TP53. 57 / 58
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"On the basis of the observation that p53 protein is methylated by SMYD2, which should lead to suppression of apoptosis, we were additionally interested in the effects of (S) -4 in combination with an apoptotic stimulus."
27075367
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"SMYD2 methylates p53 to prevent p53 from binding to its target gene promoters, and knockdown of SMYD2 enhances DNA damage-induced, p53-dependent apoptosis xref ."
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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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"Methylation of Lys370 p53 by Smyd2 reduces its binding efficiency to promoter genes, thereby repressing p53 transcriptional activity (Huang et al ., xref )."
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"Smyd2 methylation of p53 reduced p53 occupancy at two target gene promoters : p21 and mdm2, and depletion of Smyd2 ramped up p53 mediated apoptosis in response to various types of DNA damage."
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"Monomethylation of p53 by SMYD2 links SMYD2 to p53 mediated apoptosis and has been shown to contribute to tumorigenesis through inhibition of p53 transcriptional activity [17]."
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"The methylation of p53 by SMYD2 has been observed in cells by several groups."
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"The methylation of p53 by SMYD2 can result in a repression of its function, which makes the SMYD2 a potential tumor suppressor. [32] Acyl-protein thioesterases (APT) are members of a protein group involved in depalmitoylation processes."
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"These results suggested that the methylation of p53 or Rb by SMYD2 is not the principal driver of SMYD2 mediated cancer cell growth and that other SMYD2 substrates or a second genetic or epigenetic driver may be involved in the process."
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"13 This antibody was then tested on recombinant p53 protein which had been in vitro methylated by SMYD2 in a Western blot."
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"In contrast, Smyd2 overexpression resulted in marked methylation of p53 and prevented its accumulation as well as apoptotic cell death in an Hsp90 independent manner."
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"For example, Smyd2 methylates p53 (on lysine 370) which reduces its DNA-binding affinity and represses p53-mediated transcriptional regulation [ xref ]."
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"However, we confirm here that Smyd2 can methylate p53 [XREF_BIBR] and provide evidence that the methylation activity of Smyd2 is required for its anti-apoptotic effect in cardioblasts."
25014164
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"However, because p53 mutations are relatively infrequent in OCCC, SMYD2 knockdown could induce apoptosis by suppressing p53 methylation."
32934721
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"In cell-based assays, BAY598 was able to inhibit the methylation of p53 by SMYD2, and it can also lead to a slight reduction of tumor area in mice[61]."
36157542
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"SMYD2 methylates p53 and retinoblastoma protein (RB) and regulates their transactivation activity [XREF_BIBR, XREF_BIBR]."
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"Methylation of p53, HSP90, pRb, and ERalpha by SMYD2 was already shown to control the association of their binding partners (Cho et al., 2012; Huang et al., 2006; Jiang et al., 2014; Voelkel et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"SMYD2 methylates p53 and retinoblastoma protein (RB) and regulates their transactivation activity [ xref , xref ]."
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"We note that p53 plays a key role in PDAC suppression ( xref ), and SMYD2 methylates and inactivates p53 ( xref ), suggesting that this signaling module is likely important for SMYD2 functions in PDAC."
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"Biochemical characterization revealed that SMYD2 preferentially binds and methylates p53 rather than histones in-vitro [ xref , xref ]."
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"In the cell cycle, SMYD2 methylates p53 and retinoblastoma tumor suppressor (RB) [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25580534
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"On the basis of the observation that p53 protein is methylated by SMYD2, which should lead to suppression of apoptosis, we were additionally interested in the effects of ( S )- 4 in combination with an apoptotic stimulus."
27075367
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"In addition to histone proteins, SMYD2 is able to methylate p53, retinoblastoma tumor suppressor (RB), estrogen receptor α (ERα), poly(ADP-ribose) polymerase 1 (PARP1), and heat shock protein-90 (Hsp90) [ xref , xref – xref ]."
26717235
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"These data suggest that Smyd2 methylates p53 also in vivo."
25014164
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"The methylation of p53 by SMYD2 can result in a repression of its function, which makes the SMYD2 a potential tumor suppressor."
35563976
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"For example, Smyd2 methylates p53 [XREF_BIBR], retinoblastoma tumor suppressor (RB) [XREF_BIBR], heat shock protein 90 (Hsp90) [XREF_BIBR] and estrogen receptor alpha (ERalpha) [XREF_BIBR]."
25014164
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"These therapeutic efforts are primarily based on the biological connection that SMYD2 methylates the tumor suppressor protein p53, leading to inhibition of p53 function ( xref )."
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"P53 methylation by SMYD2 reduces the transactivation activity of p53 [XREF_BIBR]."
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"Interestingly, the methylation of p53 by KMT3C represses the transcriptional activation of p21 and MDM2 by p53."
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"SMYD2 methylation of p53 adhered to classical MM kinetics ( xref )."
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"SMYD2 and KMT3C can methylate both histone (H2B, H3, and H4) and nonhistone proteins p53 and Rb [XREF_BIBR, XREF_BIBR]."
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"These results suggest that methylation of p53 or Rb by SMYD2 is not the principal driver of SMYD2-mediated cancer cell growth and that other SMYD2 substrates or a second genetic or epigenetic driver may be involved."
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"Both Sirt1 and Smyd2 can also deacetylate and methylate p53 on lysines, respectively, to impede p53 from binding to its target gene promoters, such as p21, and knockdown of Smyd2 enhances DNA damage-induced and p53-dependent apoptosis [ xref , xref ]."
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"XREF_BIBR, XREF_BIBR The structural basis of p53 methylation by SMYD2 has been characterized by solving the crystal structure of a ternary complex with the cofactor product S-adenosylhomocysteine and a p53 derived substrate peptide."
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"LLY-507 inhibited SMYD2-induced p53 methylation in U2OS cells with an IC 50 of 0.6 μ m ( xref B )."
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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."
21866297
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"The methylation of p53 by SMYD2 has been observed in cells by several groups ( xref , xref , xref )."
25825497
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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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"In addition to histone proteins, SMYD2 is able to methylate p53, retinoblastoma tumor suppressor (RB), estrogen receptor alpha (ERalpha), poly (ADP-ribose) polymerase 1 (PARP1), and heat shock protein-90 (Hsp90) [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
26717235
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"These data suggest that Smyd2 methylates p53 also in vivo ."
25014164
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"These results suggest that methylation of p53 or Rb by SMYD2 is not the principal driver of SMYD2 mediated cancer cell growth and that other SMYD2 substrates or a second genetic or epigenetic driver may be involved."
25825497
sparser
"Methylation of p53, HSP90, pRb, and ERα by SMYD2 was already shown to control the association of their binding partners ( Cho et al., 2012; Huang et al., 2006; Jiang et al., 2014; Voelkel et al., 2013[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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."
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"As> 90% of HGSOC cells have p53 mutations, it is possible that SMYD2 promotes apoptosis independently of p53 methylation."
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"Tumor supressor and transcription factor p53,a major pro-apoptotic player contributes to the apoptosis of various cell types,and monomethylation of p53 by Smyd2 was reported to repress p53 transactivation.Enforced Smyd2 overexpression in cardiomyocytes prevented p53 accumulation and apoptotic cell death."
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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)."
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"Interestingly, the methylation of p53 by KMT3C represses the transcriptional activation of p21 and MDM2 by p53."
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"SMYD2 methylates p53 to prevent p53 from binding to its target gene promoters, and knockdown of SMYD2enhancesDNA damage induced, p53 dependent apoptosis 10."
29487338
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"As >90% of HGSOC cells have p53 mutations ( xref ), it is possible that SMYD2 promotes apoptosis independently of p53 methylation."
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"Another possibility is that Smyd2, being recruited to chromatin, methylates not only p53, but also histones in the vicinity of p53 binding sites [XREF_BIBR], thus inhibiting p53 binding."
24298606
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"However, we confirm here that Smyd2 can methylate p53 [ xref ] and provide evidence that the methylation activity of Smyd2 is required for its anti-apoptotic effect in cardioblasts."
25014164
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"It is known that p53 can be mono-methylated by SMYD2."
26471002
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"However, the interest in better understanding the roles of SMYD2 has grown because of recent reports indicating that SMYD2 methylates p53 and histone H3."
18065756
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"For example, Smyd2 methylates p53 [ xref ], retinoblastoma tumor suppressor (RB) [ xref ], heat shock protein 90 (Hsp90) [ xref ] and estrogen receptor alpha (ERα) [ xref ]."
25014164
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"As an upstream regulator of the p53 pathway, SMYD2 monomethylates p53 and deactivates the transcriptional activity of p53, and it is thus possible that its ability to block the p53-tumor suppressor activity is another mechanism by which SMYD2 contributes to PDAC progression."
36157542
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"It is known that p53 can be mono-methylated by SMYD2."
26471002
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"However, the interest in better understanding the roles of SMYD2 has grown because of recent reports indicating that SMYD2 methylates p53 and histone H3."
18065756