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PRMT5 methylates TP53. 60 / 62
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"These data support a mechanism wherein survival of D1T286A expressing cells is driven by and may require PRMT5-dependent methylation of p53."
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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."
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"Furthermore, PRMT5 monomethylates p53 within its oligomerization domain on a similar " GRG R / K " sequence to that found in histones, modestly influencing p53 tetramer formation and its target selection [XREF_BIBR]."
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"PRMT5 interacts with and methylates p53 at Arg333/335/337 residues, affecting the promoter specificity of p53 associated with apoptosis or cell cycle arrest ."
34006904
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"For example, H4R3 can be methylated by PRMT1, PRMT5, PRMT6, and PRMT7; xref – xref TP53 can be methylated by PRMT3 and PRMT5; xref , xref and H3R2 can be methylated by PRMT5, PRMT6, and PRMT7. xref , xref To further understand the roles of each PRMT in cell biology, highly selective and cell-active inhibitors of each PRMT are needed."
33591753
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"Among others, PRMT5 methylates P53 thereby modifying its DNA-binding activity and suppressing the expression of proapoptotic and antiproliferative genes, which contributes to lymphomagenesis xref , xref ."
36167829
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"OXR1 was also shown to stimulate PRMT5-dependent methylation of p53, which results in cell cycle arrest."
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"PRMT5 can also directly methylate p53, Rad9 (cell cycle checkpoint control protein), Fen1 (Flap endonuclease-1), and TDP (tyrosyl-DNA phosphodiesterase)(summarized in ), further corroborating the relevance of PRMT5 in DDR."
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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."
21866297
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"PRMT5 dependent methylation of p53 occurs within the p53 oligomerization domain suggesting a direct influence on p53 DNA binding and transcriptional output."
25582697
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"PRMT5 also has numerous non-histone-related functions : PRMT5 directly methylates transcription factors E2F1 and p53 to regulate their function (Cho et al., 2012; Jansson et al., 2008)."
30057274
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"They showed that PRMT5 methylates p53 in vitro , and mapped the sites of methylation using mass spectrometry of cellular p53."
19043433
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"Similar to published results using a histone H4 substrate ( xref ), D1T286A/CDK4 kinase triggered a significant increase in PRMT5-dependent methylation of p53 ( xref )."
25582697
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"PRMT5 can methylate p53 and modify its DNA binding activity, which in turn triggers a change in the p53-controlled gene expression program [ xref ]."
30613353
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"Moreover, PRMT5 regulates the expression and activity of key players in oncogenic and apoptotic signaling, and was shown to participate in stem cell maintenance. xref , xref PRMT5‐mediated H3R8 and H4R3 methylation, for example, repress the transcription of a number of tumor suppressors including RB‐family genes, ST7, and NM23, leading to increased cell survival and proliferation. xref , xref PRMT5 also directly methylates p53, PI3K, and E2F‐1, thereby influencing the transcriptional activity of these essential cell fate regulators to promote cell growth and inhibit apoptosis. xref , xref , xref Given this, PRMT5 has been attributed oncogenic functions and has recently received considerable attention as a potential therapeutic target in cancer."
30957988
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"Cyclin D1T286A and CDK4 promotes PRMT5 dependent methylation of p53."
25582697
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"OXR1 was also shown to stimulate PRMT5 dependent methylation of p53, which results in cell cycle arrest."
33384581
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"Similar to published results using a histone H4 substrate, D1T286A and CDK4 kinase triggered a significant increase in PRMT5 dependent methylation of p53 (XREF_SUPPLEMENTARY)."
25582697
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"Moreover, Prmt5 methylation of p53 modulates responses to DNA damage ( xref ), where depletion of Prmt5 triggers p53-dependent apoptosis rather arrest."
19245798
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"More recent work revealed that cyclin D1-CDK4 can inactivate p53 through PRMT5-dependent p53 methylation, thereby permitting tumor progression while maintaining wild type p53 [ xref , xref ]."
27695879
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"In conclusion, the present study, using an innovative in vivo model integrating the stress-responsive Gadd45β -luciferase transgene and inducible oncogenes (LSL-K-ras G12D and Myc ER ), uncovers two novel and significant findings: (i) normal HSPCs utilize arginine methylation of p53 by PRMT5 to orchestrate long-lasting oncogenic response. (ii) FA deficiency leads to a complete reversal of the response pattern characterized by short-lived oncogenic stress response accompanied with aberrant oncogene-induced arginine methylation of p53 resulted from a progressive decline in PRMT5 in FA HSPCs."
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"PRMT5 also induces transcriptional silencing by methylating p53 or MBD2 (methyl-CpG binding domain protein 2), altering their biochemical functions [XREF_BIBR, XREF_BIBR]."
27556302
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"One typical example is p53, which could be methylated at multiple arginine sites (Are 333, Arg 335, Arg 337) by PRMT5 and at multiple lysine sites (Lys 370, Lys 372, Lys 373, Lys 382)."
33787478
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"PRMT5-dependent methylation of p53 occurs within the p53 oligomerization domain suggesting a direct influence on p53 DNA binding and transcriptional output."
25582697
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"Likewise, PRMT5 methylation of p53 was implicated in altered nuclear localization and activity, which promotes lymphomagenesis [42]."
32743345
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"PRMT5 directed methylation of tumor suppressor p53 has been shown in cells with DNA damage [XREF_BIBR, XREF_BIBR]."
26078354
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"Second, is there an interplay of p53 arginine methylation by PRMT5 with the myriad other PTMs on p53 (ref. xref )?"
19043433
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"Arginine methylation of E2F1 and p53 by PRMT5 reportedly influences protein stability; therefore PRMT5 regulates cell cycle progression and cell death ."
25721668
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"We provide evidence for a direct link between PRMT5-dependent arginine methylation of p53, reduced expression of pro-apoptotic p53 transcriptional targets and hematologic malignancy."
25582697
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"In addition, PRMT5 directly methylates p53, thereby affecting the transcriptional activity of these essential cell fat modulators, promoting cell growth, and inhibiting apoptosis ( xref ; xref )."
34124017
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"Jansson et al. demonstrate that arginine methylation of p53 by PRMT5 regulates target gene specificity of p53 by altering promoter binding."
19450511
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"Experiments reported by Li et al describe the contribution of PRMT5-dependent methylation of p53 in the bypass of p53-dependent apoptosis [ xref ]."
26425661
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"PRMT5 can methylate p53 and modify its DNA binding activity, which in turn triggers a change in the p53-controlled gene expression program [27]."
30613353
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"As expected, PRMT5 silencing by siRNA reduced p53 methylation (XREF_SUPPLEMENTARY), along with increased p53 transcriptional activity (XREF_SUPPLEMENTARY)."
29158558
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"These data support the utilization of PRMT5 dependent methylation of p53 as an alternative to the acquisition of inactivating p53 mutations."
25582697
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"Thus, these studies defined a compromised oncogene-induced arginine methylation of p53 by PRMT5 as one mechanism for the short-lived oncogenic stress response in FA HSPCs."
27507053
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"These data support a mechanism wherein survival of D1T286A expressing cells is driven by and may require PRMT5 dependent methylation of p53."
25582697
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"The authors then set out to determine whether PRMT5 directly methylates p53."
19043433
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"A second centers on how arginine methylation of histones, E2F1 and p53 (as well as yet to be identified substrates) by PRMT5 is coordinated for neoplastic growth."
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"Downregulation of Protein Arginine Methyltransferase 5 (PRMT5) led to compromised K-ras G12D -induced arginine methylation of p53 in FANCA deficient cells, thereby demonstrating an arginine methylation dependent FA-p53 interaction, as forced expression of PRMT5 in FANCA -/- HSPCs prolonged oncogenic response and delayed leukemia development in irradiated recipient mice."
29593731
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"PRMT5 can also directly methylate p53, Rad9 (cell cycle checkpoint control protein), Fen1 (Flap endonuclease-1), and TDP (tyrosyl-DNA phosphodiesterase)(summarized in xref ), further corroborating the relevance of PRMT5 in DDR."
34052526
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"PRMT5 mediates p53 methylation, which disposes the cell to arrest rather than death."
19043433
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"44 PRMT5 interacted with and elicited p53 methylation in its oligomerization region, which resulted in alterations in the p53 response."
33675123
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"It stands to reason that PRMT5-dependent p53 arginine methylation in cancers is not just a consequence of oncogenesis, but represents a key step in initiating and maintaining this complex process."
26425661
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"For example, H4R3 can be methylated by PRMT1, PRMT5, PRMT6, and PRMT7; TP53 can be methylated by PRMT3 and PRMT5; and H3R2 can be methylated by PRMT5, PRMT6, and PRMT7."
33591753
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"Indeed, it was demonstrated that p53 methylation by PRMT5 altered some of the p53 cellular and biochemical properties in response to DNA damage."
| PMC
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"Moreover, Prmt5 methylation of p53 modulates responses to DNA damage, where depletion of Prmt5 triggers p53 dependent apoptosis rather arrest."
19245798
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"More recent research demonstrated that PRMT5 mediated arginine methylation affects the target gene specificity of p53."
29163212
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"The effects of lysine and arginine methylation on chromatin structure and gene expression have been well characterized [ xref – xref ] In the tetramerization domain, PRMT5 methylates p53 at different arginine residues (R333, R335, and R337) [ xref ], and this modifications likely inactivate p53 during lymphomagenesis and controls p53 action in cell cycle arrest (Fig.  xref ) [ xref ]."
34952583
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"The authors showed that PRMT5 methylates p53 at selected arginine residues in p53 oligomerization domain."
19528079
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"Likewise, PRMT5 methylation of p53 was implicated in altered nuclear localization and activity, which promotes lymphomagenesis [ xref ]."
32743345
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"Cyclin D1T286A/CDK4 promotes PRMT5-dependent methylation of p53."
25582697
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"They showed that PRMT5 methylates p53 in vitro, and mapped the sites of methylation using mass spectrometry of cellular p53."
19043433
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"Experiments reported by Li et al describe the contribution of PRMT5 dependent methylation of p53 in the bypass of p53 dependent apoptosis [XREF_BIBR]."
26425661
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"The PRMT5-dependent methylation of p53 at residues R333, R335 and R337 represses the p53-DNA interaction."
32379587
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"PRMT5 also has numerous non-histone-related functions: PRMT5 directly methylates transcription factors E2F1 and p53 to regulate their function ( Cho et al., 2012; Jansson et al., 2008 )."
30057274
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"PRMT5 directed methylation of p53 has been shown to occur in cells that have DNA damage, and this methylation coincided with activation of the p53 response [XREF_BIBR]."
22708516
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"These data support the utilization of PRMT5-dependent methylation of p53 as an alternative to the acquisition of inactivating p53 mutations."
25582697
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"PRMT5 directly methylates epidermal growth factor receptor (EGFR), E2F1, and p53 to promote cell survival and growth [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
27480244
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"The authors then set out to determine whether PRMT5 directly methylates p53."
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