title: E2F1-mediated apoptosis as a target of cancer therapy.
abstract: The development of cancer depends on the delicate balance between cell proliferation and programmed cell death. p16(INK4a) -cyclinD/cdk4-pRb-E2F1 is a critical pathway regulating cell proliferation in which E2F1 is an important downstream effector. Deregulated E2F1 activity due to the aberrance of the upstream components in this pathway, such as inactivation of Rb or p16, or amplification of cyclinD or cdk4, confers growth advantage to cancer cells and has thus become a hallmark of human tumors. In addition to cell proliferation control, compelling evidence indicates that E2F1 can also induce apoptosis under various cellular contexts regardless of p53 status. Given the frequent inactivation of tumor suppressor pRb and p53 in human cancers, E2F1- induced apoptosis might serve as an additional tumor surveillance mechanism to protect the organism from tumor development. E2F1-mediated apoptosis pathway is therefore emerging as a promising target for therapeutic intervention. Here, we review the recent advances in the understanding of E2F1-mediated apoptosis in cancer cells and discuss how these discoveries may expand our view of E2F1 signaling network and contribute to the development of novel therapeutic strategy.
authors.affiliation: Cancer Biology and Pharmacology, Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D004249:DNA Damage; D050687:E2F1 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050687:E2F1 Transcription Factor; D056572:Histone Deacetylase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53