Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity.
Ski interacting protein (Skip) plays an important role in the transforming activity of both v-Ski and EBNA2 (Epstein-Barr virus encoded latency protein) and is involved in EBNA2 and NotchIC activation of CBF1-repressed promoters. We have previously shown that Skip acts as a transcriptional co-activator on a number of cellular and viral promoters. Here, we report that Skip also interacts with pRb and, in cooperation with Ski, can overcome pRb-induced transcriptional repression. We show a strong and direct interaction between pRb and Skip, and we map the site of interaction to amino acid residues 171-353 of the evolutionarily conserved SNW domain of Skip. Furthermore, the combination of Skip and Ski can successfully overcome the G1 arrest and flat cell phenotype induced by pRb. Taken together, these studies suggest that one potential function of the Skip-Ski complex is to overcome the growth-suppressive activities of pRb.
Prathapam
Tulasiram
T
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012, Trieste, Italy.
Kühne
Christian
C
Banks
Lawrence
L
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D016193:G1 Phase; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D056918:Nuclear Receptor Coactivators; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors*; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; C111791:SNW1 protein, human; D014157:Transcription Factors