CDK4 regulation by TNFR1 and JNK is required for NF-kappaB-mediated epidermal growth control.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, JY; Tao, S; Kimmel, R; Khavari, PA

Published Date

  • February 7, 2005

Published In

Volume / Issue

  • 168 / 4

Start / End Page

  • 561 - 566

PubMed ID

  • 15699216

Pubmed Central ID

  • 15699216

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200411060

Language

  • eng