Ski interacts with the evolutionarily conserved SNW domain of Skip.
Ski interacting protein (Skip) has been found to bind to the highly conserved region of Ski, which is required for its transforming activity. Ski is a unique oncoprotein that is involved in inducing both transformation and differentiation. At the molecular level, Ski has been shown to exhibit either co-activator or co-repressor activity depending on the cellular and promoter context. We were interested in further elucidating the biological implications of the Ski-Skip interaction. Here we have identified the SNW domain of Skip as the interaction region for Ski. This domain of Skip is highly conserved in all the Skip homologues identified from different species. Using a series of reporter plasmids, we show that Skip is a potent transcriptional activator of many different promoters, the activity of which was also mapped to the conserved core SNW domain of the protein. Addition of excess Ski further augmented the transcriptional activities of Skip, suggesting that one of the ways in which Ski brings about transformation is by binding and cooperating with the SNW domain of Skip in transcriptional activation.
Prathapam
T
T
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012, Trieste, Italy.
Kühne
C
C
Hayman
M
M
Banks
L
L
D001665:Binding Sites / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C111791:SNW1 protein, human; D014157:Transcription Factors; C060614:SKI protein, human; D015500:Chloramphenicol O-Acetyltransferase