IndraLab

"Histone arginine methyltransferases also play critical roles in CSC biology in both solid and hematological cancers. xref Among them, protein arginine methyltransferase 5 (PRMT5) is implicated in breast CSC maintenance by controlling the expression of stemness-related TFs such as POU5F1, MYC, KLF transcription factor 4 (KLF4), and forkhead box P1 (FOXP1). xref , xref In leukemia, PRMT5 supports LSC self-renewal, survival, and tumorigenicity by promoting WNT/β-catenin signaling (an action shared with PRMT1), xref as well as by repressing the tumor protein p53 (TP53, best known as p53) system. xref Specifically, PRMT5 directly methylates p53 at arginine residues, leading to the selective repression of p53-regulated oncosuppressive target genes."

"In Fanca-/- and Fancc -/- mice, arginine methylation of p53 by PRMT5 was decreased in response to oncogenic stress [XREF_BIBR]."

"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."

"6 A physical interaction of TTC5 with Protein Methyltransferase 5 (PRMT5), which arginine methylates TP53, has been reported, 7 as has a regulatory role for TTC5 in steroid hormone signaling where it acts as a cofactor for the glucocorticoid and estrogen receptors."

"The methyltransferase PRMT5 methylates p53 at three arginine residues (333, 335, 357) within the oligomerization domain to influence the outcome of the p53 response [64] ."

"PRMT5 arginine methylation of p53 gene was required in altered nuclear localization and activation in promoting lymphomagenesis [37, 38], therefore, we speculated if PRMT5 was involved in the lipogenesis through epigenetic modification."

"PRMT5 induces arginine methylation of tumor suppressor p53 on the arginine 333,335 and 337 and affects the p53 target gene specificity, thereby escaping p53 surveillance and leading to tumorigenesis."

"In 2008, Jansson et al demonstrated that PRMT5 can methylate p53 at arginine residues 333, 335 and 337 to activate transcription of p21 and promote G 1 cell cycle arrest in response to DNA damaging agent etoposide ( xref )."

"The authors showed that PRMT5 methylates p53 at selected arginine residues in p53 oligomerization domain."

"Following DNA damage, PRMT5 methylates p53 at arginine residues R333, R335, and R337 [ xref ]."

"Arginine methylation of E2F1 and p53 by PRMT5 reportedly influences protein stability; therefore PRMT5 regulates cell cycle progression and cell death [14,22,23]."

"The methyltransferase PRMT5 methylates p53 at three arginine residues (333, 335, 357) within the oligomerization domain to influence the outcome of the p53 response [64] ."

"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."

"Jansson et al. demonstrate that arginine methylation of p53 by PRMT5 regulates target gene specificity of p53 by altering promoter binding."

"In conclusion, the present study, using an innovative in vivo model integrating the stress responsive Gadd45beta-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."

"Because PRMT5 has been shown to mediate arginine methylation of p53 to regulate its function [XREF_BIBR, XREF_BIBR], we explored the effects of AMI-1 on p53 in nude mouse CRC xenograft model."

"In addition, by stimulating PRMT5/MEP50-dependent arginine-methylation of p53, cyclin D-CDK4/6 suppresses the expression of key anti-proliferative and pro-apoptotic p53-target genes (40)."

"Apart from epigenetic modifications, PRMT5 has been shown to mediate arginine methylation of P53 to regulate its function."

"Mechanistic studies reveal that FA deficiency in HSPCs impairs oncogenic stress induced G 1 cell-cycle checkpoint, resulting from a compromised K-ras G12D -induced arginine methylation of p53 mediated by the protein arginine methyltransferase 5 (PRMT5)."