title: Transformation by v-Jun prevents cell cycle exit and promotes apoptosis in the absence of serum growth factors.
abstract: To gain insight into the mechanism of action of the v-Jun oncoprotein, we compared the growth and cell cycle behavior of normal and v-Jun-transformed fibroblasts. We show that v-Jun induces marked alterations in cell cycle regulation in both the presence and absence of serum growth factors. During asynchronous growth, v-Jun-transformed fibroblasts divide more rapidly than their normal counterparts, owing to a reduction in the length of the G1 phase of the cell cycle. When deprived of serum mitogens, normal fibroblasts exit the cycle and enter a reversible state of quiescence (G0). In contrast, v-Jun-transformed fibroblasts continue to cycle and maintain increased levels of retinoblastoma tumor suppressor protein phosphorylation and elevated expression of cell cycle-dependent markers such as cyclin A, cyclin-dependent protein kinase 2 (CDK2), and CDC2. v-Jun-transformed fibroblasts nevertheless remain wholly dependent on growth factors for cell multiplication, because cell cycle progression in the absence of serum is accompanied by high rates of apoptotic cell death. We conclude that v-Jun shares the capacity of the Myc, E1A, and E2F oncoproteins to promote both cell cycle progression and apoptosis under conditions of mitogen depletion.
authors.affiliation: Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Bearsden, Glasgow, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Clark
authors.forename: D A
authors.initials: DA
authors.lastname: Gillespie
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D005347:Fibroblasts / Q000166:cytology; D006133:Growth Substances / Q000097:blood / Q000502:physiology*; D006801:Humans; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006133:Growth Substances; D016759:Oncogene Protein p65(gag-jun); D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases