Arginine methylation-dependent regulation of ASK1 signaling by PRMT1

J. H. Cho, M. K. Lee, K. W. Yoon, J. Lee, S. G. Cho, Eui Ju Choi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is implicated in modulation of cellular processes including gene transcription. The role of PRMTs in the regulation of intracellular signaling pathways has remained obscure, however. We now show that PRMT1 methylates apoptosis signal-regulating kinase 1 (ASK1) at arginine residues 78 and 80 and thereby negatively regulates ASK1 signaling. PRMT1-mediated ASK1 methylation attenuated the H 2O 2-induced stimulation of ASK1, with this inhibitory effect of PRMT1 being abolished by replacement of arginines 78 and 80 of ASK1 with lysine. Furthermore, depletion of PRMT1 expression by RNA interference potentiated H 2O 2-induced stimulation of ASK1. PRMT1-mediated ASK1 methylation promoted the interaction between ASK1 and its negative regulator thioredoxin, whereas it abrogated the association of ASK1 with its positive regulator TRAF2. Moreover, PRMT1 depletion potentiated paclitaxel-induced ASK1 activation and apoptosis in human breast cancer cells. Together, our results indicate that arginine methylation of ASK1 by PRMT1 contributes to the regulation of stress-induced signaling that controls a variety of cellular events including apoptosis.

Original languageEnglish
Pages (from-to)859-870
Number of pages12
JournalCell Death and Differentiation
Volume19
Issue number5
DOIs
Publication statusPublished - 2012 May 1

Fingerprint

MAP Kinase Kinase Kinase 5
Methylation
Arginine
Protein-Arginine N-Methyltransferases
TNF Receptor-Associated Factor 2
Apoptosis
Thioredoxins
RNA Interference
Paclitaxel
Lysine

Keywords

  • arginine methylation
  • ASK1
  • paclitaxel
  • PRMT1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Arginine methylation-dependent regulation of ASK1 signaling by PRMT1. / Cho, J. H.; Lee, M. K.; Yoon, K. W.; Lee, J.; Cho, S. G.; Choi, Eui Ju.

In: Cell Death and Differentiation, Vol. 19, No. 5, 01.05.2012, p. 859-870.

Research output: Contribution to journalArticle

Cho, J. H. ; Lee, M. K. ; Yoon, K. W. ; Lee, J. ; Cho, S. G. ; Choi, Eui Ju. / Arginine methylation-dependent regulation of ASK1 signaling by PRMT1. In: Cell Death and Differentiation. 2012 ; Vol. 19, No. 5. pp. 859-870.
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