Characterization of an E2F1-specific binding domain in pRB and its implications for apoptotic regulation

• Published in: Oncogene Vol. 27; no. 11; pp. 1572 - 1579
• Main Authors: Julian, L M, Palander, O, Seifried, L A, Foster, J E G, Dick, F A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.03.2008; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Apoptosis - physiology; Binding Sites; Biological and medical sciences; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cancer; Cell Biology; Cell cycle; Cell cycle, cell proliferation; Cell growth; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA binding proteins; E2F protein; E2F1 protein; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Eye diseases; Flow Cytometry; Fundamental and applied biological sciences. Psychology; G1 Phase - physiology; Gene expression; Health aspects; Human Genetics; Humans; Internal Medicine; Luciferases - metabolism; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Mutagenesis; Mutants; Mutation; Oncology; Ophthalmology; original-article; Osteosarcoma - genetics; Osteosarcoma - metabolism; Osteosarcoma - pathology; Physiological aspects; Proteins; Retina; Retinoblastoma; Retinoblastoma protein; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; Transcription, Genetic; Tumor Cells, Cultured; Tumor suppressor genes; Tumors; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Canada; E2F; apoptosis; transcription; cell cycle; retinoblastoma; Human; Nervous system diseases; Retinopathy; Transcription; Malignant tumor; Carcinogenesis; Characterization; Eye disease; Regulation(control); Cell cycle; Retinoblastoma; Child; Cancer; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210803

The retinoblastoma protein (pRB) has the dual capability to negatively regulate both E2F-induced cell cycle entry and E2F1-induced apoptosis. In this report, we characterize a unique pRB–E2F1 interaction. Using mutagenesis to disrupt E2F1 binding, we find that the ability of pRB to regulate E2F1-induced apoptosis is diminished when this interaction is lost. Strikingly, this mutant form of pRB retains the ability to control E2F responsive cell cycle genes and blocks cell proliferation. These functional properties are the reciprocal of a previously described E2F binding mutant of pRB that interacts with E2F1, but lacks the ability to interact with other E2Fs. Our work shows that these distinct interactions allow pRB to separately regulate E2F-induced cell proliferation and apoptosis. This suggests a novel form of regulation whereby separate types of binding contacts between the same types of molecules can confer distinct functional outcomes.