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Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis

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Yamamura, Yasuko, Hua, Xianxin, Bergelson, Svetlana, Lodish, Harvey F.·2000·Journal of Biological Chemistry

Abstract

Transforming growth factor-beta1 (TGF-beta1) induces not only cell growth inhibition but also apoptosis in hepatocytes, myeloid cells, and epithelial cells. Although Smad proteins are identified as key signal transducers in TGF-beta1-dependent growth inhibition, their roles in the induction of apoptosis are unclear. We show here that both Smad proteins and AP-1 complex are involved in TGF-beta1 signaling for apoptosis. Overexpression of a dominant-negative Smad3 mutant or Smad7, both of which impair Smad-mediated signal transduction, inhibits TGF-beta1-dependent apoptosis. Only the JunD. FosB form of the AP-1 complex is markedly activated during TGF-beta1-dependent apoptosis. FosB substantially enhances Smad3. Smad4-dependent transcription, and dominant-negative FosB blocks TGF-beta1-dependent apoptosis but not growth inhibition. Expression of JunD.FosB enhances induction of apoptosis by TGF-beta1. Moreover, JunD.FosB binds to the 12-O-tetradecanoyl-13-acetate-responsive gene promoter element and recruits Smad3.Smad4 to form a multicomponent complex. These results suggest that Smad proteins and AP-1 complex synergize to mediate TGF-beta1-dependent apoptosis.

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Metadata

Authors
Yamamura, Y., Hua, X., Bergelson, S., & Lodish, H. F.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-11
Volume
275
Issue
46
Pages
36295-36302
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2032927685
Cited by
188
References
4
FWCI
5.75
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis. https://app.cochat.ai/papers/10.1074/jbc.m006023200
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Yamamura, Y., Hua, X., Bergelson, S., & Lodish, H. F. (2000). Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m006023200

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