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Molecular and Cellular Biology, March 2008, p. 1584-1595, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.00421-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Corepressor CtBP and Nuclear Speckle Protein Pnn/DRS Differentially Modulate Transcription and Splicing of the E-Cadherin Gene{triangledown}

Roman Alpatov,1 Yujiang Shi,3 Gustavo C. Munguba,1 Babak Moghimi,2 Jeong-Hoon Joo,1 Jorg Bungert,2 and Stephen P. Sugrue1*

Department of Anatomy and Cell Biology,1 Department of Biochemistry, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, Florida 32610,2 Division of Endocrinology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 021153

Received 11 March 2007/ Returned for modification 9 April 2007/ Accepted 26 November 2007

CtBP is a transcriptional corepressor with tumorigenic potential that targets the promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a "nuclear speckle"-associated protein involved in mRNA processing as well as transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show that CtBP can recruit Pnn to CtBP-associated complexes, resulting in Pnn-dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and Pnn can differentially modulate E-cadherin mRNA splicing, with polymerase II serving as an interface in this event. Therefore, the Pnn/CtBP functional interplay represents a novel mechanism linking the corepressor CtBP and Pnn to the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our findings implicate the existence of the molecular switches involved in tumorigenesis, which coordinate promoter-specific events and mRNA processing, by serving as bridging elements between the regulatory complexes both at gene promoters and within the mRNA splicing machineries.

* Corresponding author. Mailing address: Department of Anatomy and Cell Biology, University of Florida College of Medicine, 1600 SW Archer Road, Box 100235, Gainesville, FL 32610. Phone: (352) 392-3569. Fax: (352) 392-3305. E-mail: Sugrue{at}anatomy.med.ufl.edu

{triangledown} Published ahead of print on 17 December 2007.

Molecular and Cellular Biology, March 2008, p. 1584-1595, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.00421-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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