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

By G. Wildey, S. Patil, P. Howe. Journal of Biological Chemistry, 2003

88 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/d61d63035f9dbb169e657dfbeaed44f250cb3995