title: Coordinated regulation of p31(Comet) and Mad2 expression is required for cellular proliferation.
abstract: p31(Comet) is a well-known interacting partner of the spindle assembly checkpoint (SAC) effector molecule Mad2. At the molecular level it is well established that p31(Comet) promotes efficient mitotic exit, specifically the metaphase-anaphase transition, by antagonizing Mad2 function. However, there is little knowledge of how p31(Comet) is regulated or the physiological importance of controlling p31(Comet). Here, we show that the Rb-E2F pathway regulates p31(Comet) expression. In multiple tumor types (including breast and lung) p31(Comet) expression is increased along with Mad2. Expression of this antagonist-target pair is coordinated in cells and correlated in cancer. Moreover, a narrow range of p31(Comet):Mad2 ratios is compatible with cellular viability. Our data suggest that coordinate regulation is important for the outgrowth of oncogenic cell populations. Our findings suggest that altered p31(Comet):Mad2 expression ratios may provide new insight into altered SAC function and the generation of chromosomal instability in tumors.
authors.affiliation: Department of Cancer Biology; Lerner Research Institute; Cleveland, OH USA.
authors.forename: Dipali A
authors.initials: DA
authors.lastname: Date
authors.affiliation: Department of Cancer Biology; Lerner Research Institute; Cleveland, OH USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Burrows
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine; Lerner Research Institute; Cleveland, OH USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Venere
authors.affiliation: Department of Pathology; Case Western Reserve University; Cleveland, OH USA; Case Comprehensive Cancer Center; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Jackson
authors.affiliation: Department of Cancer Biology; Lerner Research Institute; Cleveland, OH USA; Case Comprehensive Cancer Center; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Summers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D050684:E2F Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D064246:Mad2 Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D050684:E2F Transcription Factors; C577697:MAD2L1 protein, human; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein
keywords: E2F; Mad2; Rb; cancer; cell cycle; p31Comet; spindle assembly checkpoint