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Smurf2 Is a Ubiquitin E3 Ligase Mediating Proteasome-dependent Degradation of Smad2 in Transforming Growth Factor-β Signaling

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Lin, Xia, Liang, Min, Feng, Xin-Hua·2000·Journal of Biological Chemistry

Abstract

Smads are important intracellular signaling effectors for transforming growth factor-beta (TGF-beta) and related factors. Proper TGF-beta signaling requires precise control of Smad functions. In this study, we have identified a novel HECT class ubiquitin E3 ligase, designated Smurf2, that negatively regulates Smad2 signaling. In both yeast two-hybrid and in vitro binding assays, we found that Smurf2 could interact with receptor-activated Smads (R-Smads), including Smad1, Smad2, and Smad3 but not Smad4. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad1 and Smad2 but not Smad3 or Smad4. Significantly, Smurf2 displayed preference to Smad2 as its target for degradation. Furthermore, Smurf2 exhibited higher binding affinity to activated Smad2 upon TGF-beta stimulation. The ability of Smurf2 to promote Smad2 destruction required the HECT catalytic activity of Smurf2 and depended on the proteasome-dependent pathway. Consistent with these results, Smurf2 potently reduced the transcriptional activity of Smad2. These data suggest that a ubiquitin/proteasome-dependent mechanism is important for proper regulation of TGF-beta signaling.

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Metadata

Authors
Lin, X., Liang, M., & Feng, X.-H.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-11
Volume
275
Issue
47
Pages
36818-36822
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1988810849
Cited by
489
References
36
FWCI
8.34
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Smurf2 Is a Ubiquitin E3 Ligase Mediating Proteasome-dependent Degradation of Smad2 in Transforming Growth Factor-β Signaling. https://app.cochat.ai/papers/10.1074/jbc.c000580200
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Lin, X., Liang, M., & Feng, X.-H. (2000). Smurf2 Is a Ubiquitin E3 Ligase Mediating Proteasome-dependent Degradation of Smad2 in Transforming Growth Factor-β Signaling. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c000580200

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