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BCL6 Represses Smad Signaling in Transforming Growth Factor-β Resistance

¹ Michael E. DeBakey Department of Surgery and ² Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas

Requests for reprints: Michael E. DeBakey, Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Room 139D, Houston, TX 77030. Phone: 713-798-4899; Fax: 713-798-4093; E-mail: xialin{at}bcm.edu.

Key Words: Oncogene • Smad • tumor suppressor • signal transduction • transcription

Transforming growth factor-β (TGF-β) controls a wide spectrum of cellular processes. Deregulation of TGF-β signaling contributes to the pathogenesis of many diseases including cancer and autoimmune diseases. TGF-β signaling is generally mediated through intracellular signal transducers and transcription factors called Smads. Herein, we have identified the oncoprotein BCL6 as a transcriptional corepressor of tumor suppressor Smad4. BCL6 physically interacts with Smad3 and Smad4, disrupts the Smad-p300 interaction, and represses the transcriptional activity of Smad4. In accordance, B-cell lymphoma cells with a high expression level of BCL6 were found to be refractory to TGF-β antiproliferative response, whereas knockdown of BCL6 expression in B-cell lymphoma cells partially restores the TGF-β responses. This study provides strong evidence that overexpression of BCL6 contributes to TGF-β resistance in B-cell lymphoma. [Cancer Res 2008;68(3):783–9]