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Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis.
J Biol Chem. 2000 Nov 17; 275(46):36295-302.JB

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.

Authors+Show Affiliations

Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. yama.mbch@med.tmd.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10942775

Citation

Yamamura, Y, et al. "Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-beta -dependent Apoptosis." The Journal of Biological Chemistry, vol. 275, no. 46, 2000, pp. 36295-302.
Yamamura Y, Hua X, Bergelson S, et al. Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis. J Biol Chem. 2000;275(46):36295-302.
Yamamura, Y., Hua, X., Bergelson, S., & Lodish, H. F. (2000). Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis. The Journal of Biological Chemistry, 275(46), 36295-302.
Yamamura Y, et al. Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-beta -dependent Apoptosis. J Biol Chem. 2000 Nov 17;275(46):36295-302. PubMed PMID: 10942775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis. AU - Yamamura,Y, AU - Hua,X, AU - Bergelson,S, AU - Lodish,H F, PY - 2000/8/16/pubmed PY - 2001/2/28/medline PY - 2000/8/16/entrez SP - 36295 EP - 302 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 275 IS - 46 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10942775/Critical_role_of_Smads_and_AP_1_complex_in_transforming_growth_factor_beta__dependent_apoptosis_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=10942775 DB - PRIME DP - Unbound Medicine ER -