DOI: 10.1093/embo-reports/kvf024. Jab1 antagonizes TGF‐β signaling by inducing Smad4 degradation

Jab1 antagonizes TGF‐β signaling by inducing Smad4 degradation

10.1093/embo-reports/kvf024

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

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.

Bibliography

Wan, M., Cao, X., Wu, Y., Bai, S., Wu, L., Shi, X., Wang, N., & Cao, X. (2002). Jab1 antagonizes TGFâÎ² signaling by inducing Smad4 degradation. EMBO Reports, 3(2), 171â176. Portico.

Authors 8

Mei Wan (first)
Xuesong Cao (additional)
Yalei Wu (additional)
Shuting Bai (additional)
Liyu Wu (additional)
Xingming Shi (additional)
Ning Wang (additional)
Xu Cao (additional)

References 31 Referenced 136

Dates

Type	When
Created	23 years ago (July 26, 2002, 6:37 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:53 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 2:45 p.m.)
Issued	23 years, 6 months ago (Feb. 1, 2002)
Published	23 years, 6 months ago (Feb. 1, 2002)
Published Online	23 years, 6 months ago (Feb. 1, 2002)
Published Print	23 years, 6 months ago (Feb. 1, 2002)

Funders 0

None

BibTeX

@article{Wan_2002, title={Jab1 antagonizes TGF‐β signaling by inducing Smad4 degradation}, volume={3}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kvf024}, DOI={10.1093/embo-reports/kvf024}, number={2}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Wan, Mei and Cao, Xuesong and Wu, Yalei and Bai, Shuting and Wu, Liyu and Shi, Xingming and Wang, Ning and Cao, Xu}, year={2002}, month=feb, pages={171–176} }

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