| First Author | Wisdom R | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 1 | Pages | 188-97 |
| PubMed ID | 9878062 | Mgi Jnum | J:51909 |
| Mgi Id | MGI:1327105 | Doi | 10.1093/emboj/18.1.188 |
| Citation | Wisdom R, et al. (1999) c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J 18(1):188-97 |
| abstractText | c-Jun is a component of the transcription factor AP-1, which is activated by a wide variety of extracellular stimuli. The regulation of c-Jun is complex and involves both increases in the levels of c-Jun protein as well as phosphorylation of specific serines (63 and 73) by Jun N-terminal kinase (JNK). We have used fibroblasts derived from c-Jun null embryos to define the role of c-Jun in two separate processes: cell growth and apoptosis. We show that in fibroblasts, c-Jun is required for progression through the G1 phase of the cell cycle; c-Jun-mediated G1 progression occurs by a mechanism that involves direct transcriptional control of the cyclin D1 gene, establishing a molecular link between growth factor signaling and cell cycle regulators. In addition, c-Jun protects cells from UV-induced cell death and cooperates with NF-kappaB to prevent apoptosis induced by tumor necrosis factor alpha (TNFalpha). c-Jun mediated G1 progression is independent of phosphorylation of serines 63/73; however, protection from apoptosis in response to UV, a potent inducer of JNK/SAP kinase activity, requires serines 63/73. The results reveal critical roles for c-Jun in two different cellular processes and show that different extracellular stimuli can target c-Jun by distinct biochemical mechanisms. |
