title: Retinoblastoma tumor suppressor and genome stability.
abstract: Retinoblastoma gene (Rb) is the prototype of tumor suppressors. Germline mutation in the retinoblastoma gene is susceptible to cancer and reintroduction of wild-type Rb is able to suppress neoplastic phenotypes. The fundamental cellular functions of Rb in the control of cell growth and differentiation are important for its tumor suppression. In general, cancer susceptibility caused by inactivation of a tumor suppressor gene results from genome instability. Accordingly, Rb may function in the maintenance of chromosome stability by influencing mitotic progression, faithful chromosome segregation, and structural remodeling of mitotic chromosomes. Rb is also implicated in the regulation of replication machinery and in the control of cell cycle checkpoints in response to DNA damage, further supporting such a role for Rb. Moreover, the mechanistic basis for Rb-mediated transcriptional repression has revealed its connection to global chromatin remodeling. It is likely that Rb suppresses tumor formation by virtue of its multiple biological activities, and a theme throughout its multiple cellular functions is its central role in controlling activities that involve chromatin remodeling. A model in which Rb controls global genome fluidity is thus proposed. Finally, a recent study provides direct evidence indicating that loss of Rb function leads to genome instability. Therefore, tumor suppressors have a common role in the maintenance of genome stability, and such a role may be pivotal for their functions in tumor suppression.
authors.affiliation: Department of Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 78245, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002503:Centromere / Q000502:physiology / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D003598:Cytoskeletal Proteins; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D016161:Genes, Retinoblastoma; D018816:Genes, cdc; D016678:Genome; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D008938:Mitosis / Q000502:physiology; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C120529:NDC80 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein