title: MDM2 overexpression, activation of signaling networks, and cell proliferation.
abstract: Frequent overexpression of MDM2 in human cancers suggests that the protein confers a survival advantage to cancer cells. However, overexpression of MDM2 in normal cells seems to restrict cell proliferation. This review discusses the cell growth regulatory functions of MDM2 in normal and genetically defective cells to assess how cancer cells evade the growth-restricting consequence of MDM2 overexpression. Similar to oncoproteins that induce a DNA damage response and oncogene induced senescence in non-transformed cells, MDM2 induces G1-arrest and intra-S phase checkpoint responses that control untimely DNA replication in the face of genetic challenges.
authors.affiliation: Department of Biochemistry and Molecular Biology, and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298, USA, spdeb@vcu.edu.
authors.forename: Swati Palit
authors.initials: SP
authors.lastname: Deb
authors.forename: Shilpa
authors.initials: S
authors.lastname: Singh
authors.forename: Sumitra
authors.initials: S
authors.lastname: Deb
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016213:Cyclins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt