Regulation of Transcription by a Protein Methyltransferase

Abstract

The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.

The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action

“…There are three related 160-kDa proteins, SRC-1 (steroid receptor co-activator-1), TIF-2 (transcriptional intermediary factor) and RAC3 (receptor-associated co-activator-3), encoded by separate genes, which form the SRC or p160 family of co-activators (Xu and Qingtian, 2003). The molecular mechanism by which co-activators exert the chromatin remodeling and transcriptional activation involves the histone acetyltransferase activity that SRC-1 and RAC3 have at their C-terminal domain (Spencer et al, 1997;Glass and Rosenfeld, 2000) such as the recruitment of other general co-activators with enzymatic activity like CBP (CREB-binding protein)/p300, p/CAF, CARM-1 and PRMT1 (Chen et al, 1999;Wang et al, 2001).…”

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

“…Based on their reaction product specificity, these enzymes are divided into two major classes: type I PRMTs promote the formation of u-monomethylarginine and asymmetric u-N G ,N G -dimethylarginine (aDMA), and type II PRMTs catalyse the formation of u-monomethylarginine and symmetric u-N G ,N G -dimethylarginine (sDMA) [1]. In mammals, six type I PRMT enzymes, such as PRMT1 [2], PRMT2 [3], PRMT3 [4], CARM1 (PRMT4) [5], PRMT6 [6] and PRMT8, have been identified, and type II enzymes identified to date include the Janus kinase-binding protein JBP1/PRMT5 [7], and PRMT7 [8,9]. The recently identified FBXO11/PRMT9 should belong to type II PRMT family although it contains a unique N-terminal F-box domain that does not appear in the other known PRMT enzymes [10].…”

“…Arginine methylation by PRMTs has been reported to regulate signal transduction [16e20], transcription [5], RNA transport [21,22], and possibly splicing [23]. PRMT1 is the predominant and essential arginine methyltransferases in human cell, responsible for at least 85% of all arginine methylation reactions [24].…”

Modulation of the Cyclin-Dependent Kinase Inhibitor p21WAF1/Cip1 Gene by Zac1 through the Antagonistic Regulators p53 and Histone Deacetylase 1 in HeLa Cells

“…Various Zac1 coding regions were generated by PCR and subcloned into the EcoRI and XhoI sites of the pSG5.HA vector, which has promoters for expression in vitro and in mammalian cells and provides a NH 2 -terminal HA-tag for the expressed protein (48), or into the EcoRI and SalI sites of the pM vector (Clontech), a vector for expression of Gal4-DBD fusion proteins from a constitutive SV40 early promoter. Plasmid DNA encoding the pcDNA3.1.HDAC1.myc (49) was a gift from Dr. M.A.…”