Smad3 Potentiates Transforming Growth Factor β (TGFβ)-induced Apoptosis and Expression of the BH3-only Protein Bim in WEHI 231 B Lymphocytes*

Transforming growth factor-β (TGFβ) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFβ-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFβ-induced responses. We also demonstrate that TGFβ induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte cell line, Ba/F3. Enhanced expression of Bim protein induced by TGFβ is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFβ-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFβ, and also suggest that the TGFβ−specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.

• Publication year

  2003

• Venue

  Journal of Biological Chemistry

• Publication date

  2003-05-16

• Fields of study

  Biology, Chemistry

• Identifiers
  DOI 10.1074/jbc.M211958200
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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