First Author | Zhang JY | Year | 2005 |
Journal | J Cell Biol | Volume | 168 |
Issue | 4 | Pages | 561-6 |
PubMed ID | 15699216 | Mgi Jnum | J:129435 |
Mgi Id | MGI:3769272 | Doi | 10.1083/jcb.200411060 |
Citation | Zhang JY, et al. (2005) CDK4 regulation by TNFR1 and JNK is required for NF-kappaB-mediated epidermal growth control. J Cell Biol 168(4):561-6 |
abstractText | Nuclear factor kappaB (NF-kappaB) mediates homeostatic growth inhibition in the epidermis, and a loss of NF-kappaB function promotes proliferation and oncogenesis. To identify mechanisms responsible for these effects, we impaired NF-kappaB action in the epidermis by three different genetic approaches, including conditional NF-kappaB blockade. In each case, epidermal hyperplasia was accompanied by an increase in both protein levels and tissue distribution of the G1 cell cycle kinase, CDK4. CDK4 up-regulation required intact TNFR1 and c-Jun NH2-terminal kinase (JNK) function. Cdk4 gene deletion concomitant with conditional NF-kappaB blockade demonstrated that CDK4 is required for growth deregulation. Therefore, epidermal homeostasis depends on antagonist regulation of CDK4 expression by NF-kappaB and TNFR1/JNK. |