title: Deregulation of cyclin E meets dysfunction in p53: closing the escape hatch on breast cancer.
abstract: In this review, we focus on pathways intersecting through p53 and cyclin E, highlighting how oncogenic effects of cyclin E deregulation, especially overexpression of shortened or low molecular weight (LMW) forms of cyclin E protein, are amplified by loss of regulatory control through p53 to promote tumor development. Expression of cyclin E protein promotes progression into S-phase, an activity opposed by p53-regulated activation of checkpoint controls or apoptosis. Loss of p53 function is an escape hatch by which tumor cells, initiated by a number of means including cyclin E deregulation, can avoid cell cycle arrest or cell death and progress through further stages of unchecked deregulation and growth. To determine how this escape hatch is opened and, ultimately, how to close it, we must understand the networks of normal signaling and processing in a cell and where they intersect.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michelle Craig
authors.initials: MC
authors.lastname: Barton
authors.forename: Said
authors.initials: S
authors.lastname: Akli
authors.forename: Khandan
authors.initials: K
authors.lastname: Keyomarsi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D002453:Cell Cycle / Q000502:physiology; D019927:Cyclin E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008970:Molecular Weight; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2