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Molecular and Cellular Biology, December 2003, p. 9081-9093, Vol. 23, No. 24
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.24.9081-9093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Smad6 Recruits Transcription Corepressor CtBP To Repress Bone Morphogenetic Protein-Induced Transcription

Xia Lin,1,2* Yao-Yun Liang,1,2 Baohua Sun,1,2 Min Liang,1,2 Yujiang Shi,3 F. Charles Brunicardi,1 Yang Shi,3 and Xin-Hua Feng1,2*

Michael E. DeBakey Department of Surgery,1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030,2 Department of Pathology, Harvard Medical School, Boston, Massachusetts 021153

Received 28 January 2003/ Returned for modification 20 March 2003/ Accepted 3 September 2003

Smad6 and Smad7 are inhibitory Smads induced by transforming growth factor ß-Smad signal transduction pathways in a negative-feedback mechanism. Previously it has been thought that inhibitory Smads bind to the type I receptor and block the phosphorylation of receptor-activated Smads, thereby inhibiting the initiation of Smad signaling. Conversely, few studies have suggested the possible nuclear functions of inhibitory Smads. Here, we present compelling evidence demonstrating that Smad6 repressed bone morphogenetic protein-induced Id1 transcription through recruiting transcriptional corepressor C-terminal binding protein (CtBP). A consensus CtBP-binding motif, PLDLS, was identified in the linker region of Smad6. Our findings show that mutation in the motif abolished the Smad6 binding to CtBP and subsequently its repressor activity of transcription. We conclude that the nuclear functions and physical interaction of Smad6 and CtBP provide a novel mechanism for the transcriptional regulation by inhibitory Smads.

* Corresponding author. Mailing address for Xia Lin: Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Room 131D, Houston, TX 77030. Phone: (713) 798-4899. Fax: (713) 798-4093. E-mail: xialin{at}bcm.tmc.edu. Mailing address for Xin-Hua Feng: Department of Molecular & Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Room 137D, Houston, TX 77030. Phone: (713) 798-4756. Fax: (703) 798-4093. E-mail: xfeng{at}bcm.tmc.edu.

Molecular and Cellular Biology, December 2003, p. 9081-9093, Vol. 23, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.24.9081-9093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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