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 language | English |
|---|---|
| Pages (from-to) | 1518-1528 |
| Number of pages | 11 |
| Journal | Cell Death and Differentiation |
| Volume | 14 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2007 Aug 1 |
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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 journal › Article
}
TY - JOUR
T1 - Positive regulation of ASK1-mediated c-Jun NH2-terminal kinase signaling pathway by the WD-repeat protein Gemin5
AU - Kim, E. K.
AU - Noh, K. T.
AU - Yoon, J. H.
AU - Cho, J. H.
AU - Yoon, K. W.
AU - Dreyfuss, G.
AU - Choi, Eui Ju
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34447633213&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447633213&partnerID=8YFLogxK
U2 - 10.1038/sj.cdd.4402157
DO - 10.1038/sj.cdd.4402157
M3 - Article
VL - 14
SP - 1518
EP - 1528
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 8
ER -