Abstract
Tumor suppressor Smad4 is the common signaling effector in the transforming growth factor β (TGF-β) superfamily. Phosphorylated regulatory Smads (R-Smads) interact with Smad4, and the complex translocates into the nucleus to regulate gene transcription. Proper TGF-β signaling requires precise control of Smad functions. Smurfs have been shown to mediate the degradation of R-Smads but not the common-partner Smad4. We report a novel mechanism of Smad4 degradation. Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation. Jab1 was initially identified as a co-activator of c-Jun, and it also induces degradation of cell cycle inhibitor p27 and tumor suppressor p53. Ectopic expression of Jab1 decreased endogenous Smad4 steady-state levels. The 26S proteasome inhibitors lactacystin and MG132 reduced the degradation rate of Smad4 protein. Examination of the effects of JAB1-induced Smad4 degradation indicates that Jab1 inhibited TGF-β-induced gene transcription. Our data suggest that Jab1 antagonizes TGF-β function by inducing degradation of Smad4 through a distinct degradation pathway.
Original language | English (US) |
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Pages (from-to) | 171-176 |
Number of pages | 6 |
Journal | EMBO Reports |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Jan 1 2002 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Jab1 antagonizes TGF-β signaling by inducing Smad4 degradation. / Wan, Mei; Cao, Xuesong; Wu, Yalei; Bai, Shuting; Wu, Liyu; Shi, Xing Ming; Wang, Ning; Cao, Xu.
In: EMBO Reports, Vol. 3, No. 2, 01.01.2002, p. 171-176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Jab1 antagonizes TGF-β signaling by inducing Smad4 degradation
AU - Wan, Mei
AU - Cao, Xuesong
AU - Wu, Yalei
AU - Bai, Shuting
AU - Wu, Liyu
AU - Shi, Xing Ming
AU - Wang, Ning
AU - Cao, Xu
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Tumor suppressor Smad4 is the common signaling effector in the transforming growth factor β (TGF-β) superfamily. Phosphorylated regulatory Smads (R-Smads) interact with Smad4, and the complex translocates into the nucleus to regulate gene transcription. Proper TGF-β signaling requires precise control of Smad functions. Smurfs have been shown to mediate the degradation of R-Smads but not the common-partner Smad4. We report a novel mechanism of Smad4 degradation. Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation. Jab1 was initially identified as a co-activator of c-Jun, and it also induces degradation of cell cycle inhibitor p27 and tumor suppressor p53. Ectopic expression of Jab1 decreased endogenous Smad4 steady-state levels. The 26S proteasome inhibitors lactacystin and MG132 reduced the degradation rate of Smad4 protein. Examination of the effects of JAB1-induced Smad4 degradation indicates that Jab1 inhibited TGF-β-induced gene transcription. Our data suggest that Jab1 antagonizes TGF-β function by inducing degradation of Smad4 through a distinct degradation pathway.
AB - Tumor suppressor Smad4 is the common signaling effector in the transforming growth factor β (TGF-β) superfamily. Phosphorylated regulatory Smads (R-Smads) interact with Smad4, and the complex translocates into the nucleus to regulate gene transcription. Proper TGF-β signaling requires precise control of Smad functions. Smurfs have been shown to mediate the degradation of R-Smads but not the common-partner Smad4. We report a novel mechanism of Smad4 degradation. Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation. Jab1 was initially identified as a co-activator of c-Jun, and it also induces degradation of cell cycle inhibitor p27 and tumor suppressor p53. Ectopic expression of Jab1 decreased endogenous Smad4 steady-state levels. The 26S proteasome inhibitors lactacystin and MG132 reduced the degradation rate of Smad4 protein. Examination of the effects of JAB1-induced Smad4 degradation indicates that Jab1 inhibited TGF-β-induced gene transcription. Our data suggest that Jab1 antagonizes TGF-β function by inducing degradation of Smad4 through a distinct degradation pathway.
UR - http://www.scopus.com/inward/record.url?scp=0036198412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036198412&partnerID=8YFLogxK
U2 - 10.1093/embo-reports/kvf024
DO - 10.1093/embo-reports/kvf024
M3 - Article
C2 - 11818334
AN - SCOPUS:0036198412
VL - 3
SP - 171
EP - 176
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 2
ER -