Jab1 antagonizes TGF-β signaling by inducing Smad4 degradation

Mei Wan, Xuesong Cao, Yalei Wu, Shuting Bai, Liyu Wu, Xing Ming Shi, Ning Wang, Xu Cao

Research output: Contribution to journalArticle

128 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)171-176
Number of pages6
JournalEMBO Reports
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2002

Fingerprint

Transforming Growth Factors
Degradation
Smad4 Protein
Proteasome Inhibitors
Ubiquitination
Transcription
Genes
Tumors
Neoplasms
Cell Cycle
Corrosion inhibitors
Cells

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 journalArticle

Wan, M, Cao, X, Wu, Y, Bai, S, Wu, L, Shi, XM, Wang, N & Cao, X 2002, 'Jab1 antagonizes TGF-β signaling by inducing Smad4 degradation', EMBO Reports, vol. 3, no. 2, pp. 171-176. https://doi.org/10.1093/embo-reports/kvf024
Wan, Mei ; Cao, Xuesong ; Wu, Yalei ; Bai, Shuting ; Wu, Liyu ; Shi, Xing Ming ; Wang, Ning ; Cao, Xu. / Jab1 antagonizes TGF-β signaling by inducing Smad4 degradation. In: EMBO Reports. 2002 ; Vol. 3, No. 2. pp. 171-176.
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