Positive regulation of ASK1-mediated c-Jun NH2-terminal kinase signaling pathway by the WD-repeat protein Gemin5

E. K. Kim, K. T. Noh, J. H. Yoon, J. H. Cho, K. W. Yoon, G. Dreyfuss, Eui Ju Choi

Research output: Contribution to journalArticle

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Abstract

Gemin5 is a 170-kDa WD-repeat-containing protein that was initially identified as a component of the survival of motor neurons (SMN) complex. We now show that Gemin5 facilitates the activation of apoptosis signal-regulating kinase 1 (ASK1) and downstream signaling. Gemin5 physically interacted with ASK1 as well as with the downstream kinases SEK1 and c-Jun NH2-terminal kinase (JNK1), and it potentiated the H2O2-induced activation of each of these kinases in intact cells. Moreover, Gemin5 promoted the binding of ASK1 to SEK1 and to JNK1, as well as the ASK1-induced activation of JNK1. In comparison, Gemin5 did not physically associate with MKK7, MKK3, MKK6, or p38. Furthermore, depletion of endogenous Gemin5 by RNA interference (RNAi) revealed that Gemin5 contributes to the activation of ASK1 and JNK1, and to apoptosis induced by H2O2 and tumor necrosis factor-α (TNFα) in HeLa cells. Together, our results suggest that Gemin5 functions as a scaffold protein for the ASK1-JNK1 signaling module and thereby potentiates ASK1-mediated signaling events.

Original languageEnglish
Pages (from-to)1518-1528
Number of pages11
JournalCell Death and Differentiation
Volume14
Issue number8
DOIs
Publication statusPublished - 2007 Aug 1

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SMN Complex Proteins
MAP Kinase Kinase Kinase 5
JNK Mitogen-Activated Protein Kinases
Phosphotransferases
RNA Interference
WD40 Repeats
HeLa Cells
Proteins
Tumor Necrosis Factor-alpha
Apoptosis

ASJC Scopus subject areas

  • Cell Biology

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Positive regulation of ASK1-mediated c-Jun NH2-terminal kinase signaling pathway by the WD-repeat protein Gemin5. / Kim, E. K.; Noh, K. T.; Yoon, J. H.; Cho, J. H.; Yoon, K. W.; Dreyfuss, G.; Choi, Eui Ju.

In: Cell Death and Differentiation, Vol. 14, No. 8, 01.08.2007, p. 1518-1528.

Research output: Contribution to journalArticle

Kim, E. K. ; Noh, K. T. ; Yoon, J. H. ; Cho, J. H. ; Yoon, K. W. ; Dreyfuss, G. ; Choi, Eui Ju. / Positive regulation of ASK1-mediated c-Jun NH2-terminal kinase signaling pathway by the WD-repeat protein Gemin5. In: Cell Death and Differentiation. 2007 ; Vol. 14, No. 8. pp. 1518-1528.
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