title: Cooperative effects of genes controlling the G(2)/M checkpoint.
abstract: It is believed that multiple effectors independently control the checkpoints permitting transitions between cell cycle phases. However, this has not been rigorously demonstrated in mammalian cells. The p53-induced genes p21 and 14-3-3sigma are each required for the G(2) arrest and allow a specific test of this fundamental tenet. We generated human cells deficient in both p21 and 14-3-3sigma and determined whether the double knockout was more sensitive to DNA damage than either single knockout. p21(-/-) 14-3-3sigma(-/-) cells were significantly more sensitive to DNA damage or to the exogenous expression of p53 than cells lacking only p21 or only 14-3-3sigma. Thus, p21 and 14-3-3sigma play distinct but complementary roles in the G(2)/M checkpoint, and help explain why genes at the nodal points of growth arrest pathways, like p53, are the targets of mutation in cancer cells.
authors.affiliation: Howard Hughes Medical Institute and Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Chan
authors.forename: P M
authors.initials: PM
authors.lastname: Hwang
authors.forename: H
authors.initials: H
authors.lastname: Hermeking
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D048948:14-3-3 Proteins; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D016195:G2 Phase / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase
chemical_list: D048948:14-3-3 Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D014446:Tyrosine 3-Monooxygenase