Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene.
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.
Alpatov
Roman
R
Department of Anatomy and Cell Biology, 1600 SW Archer Rd., University of Florida College of Medicine, Gainesville, FL 32610-0235, USA.
Munguba
Gustavo Costa
GC
Caton
Paul
P
Joo
Jeong Hoon
JH
Shi
Yang
Y
Shi
Yujiang
Y
Hunt
Marguerite E
ME
Sugrue
Stephen P
SP
D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004285:Dogs; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D015820:Cadherins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C102646:PNN protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D012313:RNA; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D008156:Luciferases; D005982:Glutathione Transferase