A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis.
Prohibitin is a potential tumor suppressor protein that can repress E2F-mediated transcription and arrest cell proliferation. We had shown previously that prohibitin could bind to the Rb protein as well as E2F and this binding was necessary to suppress cell proliferation. Here we show that the E2F1 binding domain of prohibitin has the potential to fold into a coiled-coil structure. This coiled-coil domain by itself could physically interact with E2F1 and block its transcriptional activity. Like full-length prohibitin, the coiled-coil domain also recruited histone deacetylase 1 to repress E2F1. The coiled-coil domain also exhibited growth suppressive properties and we observed a 64% reduction in colony numbers when transfected into T47D cells. Interestingly, a synthetic peptide corresponding to the coiled-coil domain induced apoptosis in four different human cell lines. It is possible that agents that can mimic this peptide would be of value in controlling proliferative disorders.
Joshi
Bharat
B
Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL 33612, USA.
Ko
Danette
D
Ordonez-Ercan
Dalia
D
Chellappan
Srikumar P
SP
D017209:Apoptosis; D001665:Binding Sites; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D000091402:Prohibitins; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012097:Repressor Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors