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Molecular and Cellular Biology, December 2004, p. 10223-10235, Vol. 24, No. 23
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.23.10223-10235.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Nuclear Speckle-Associated Protein Pnn/DRS Binds to the Transcriptional Corepressor CtBP and Relieves CtBP- Mediated Repression of the E-Cadherin Gene

Roman Alpatov,1 Gustavo Costa Munguba,1 Paul Caton,1 Jeong Hoon Joo,1 Yang Shi,2 Yujiang Shi,2 Marguerite E. Hunt,1 and Stephen P. Sugrue1*

Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida,1 Department of Pathology, Harvard Medical School, Boston, Massachusetts2

Received 20 April 2004/ Returned for modification 11 June 2004/ Accepted 7 September 2004

Previously, we have shown that pinin/DRS (Pnn), a 140-kDa nuclear and cell adhesion-related phosphoprotein, is involved in the regulation of cell adhesion and modulation of the activity of multiple tumor suppressor genes. In the nucleus Pnn is concentrated in the "nuclear speckles," zones of accumulation of transcriptional and mRNA splicing factors, where Pnn is involved in mRNA processing. Alternatively, other roles of Pnn in gene regulation have not yet been established. By utilizing in vitro pull-down assays, in vivo interaction studies, and immunofluorescence in combination with overexpression and RNA interference experiments, we present evidence that Pnn interacts with the known transcriptional corepressor CtBP1. As a consequence of this interaction Pnn was capable of relieving the CtBP1-mediated repression of E-cadherin promoter activity. Our results suggest that the interaction of Pnn with the corepressor CtBP1 may modulate repression of transcription by CtBP1. This interaction may reflect the existence of coupling factors involved in CtBP-mediated transcriptional regulation and mRNA processing events.

* Corresponding author. Mailing address: Department of Anatomy and Cell Biology, 1600 SW Archer Rd., University of Florida College of Medicine, Gainesville, FL 32610-0235. Phone: (352) 392-3569. Fax: (352) 392-3305. E-mail: sugrue{at}anatomy.med.ufl.edu.

Molecular and Cellular Biology, December 2004, p. 10223-10235, Vol. 24, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.23.10223-10235.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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