PKCη promotes a proliferation to differentiation switch in keratinocytes via upregulation of p27Kip1 mRNA through suppression of JNK/c-Jun signaling under stress conditions
Open Access
- 19 May 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 2 (5), e157
- https://doi.org/10.1038/cddis.2011.40
Abstract
To maintain epidermal homeostasis, the balance between keratinocyte proliferation and differentiation is tightly controlled. However, the molecular mechanisms underlying this balance remain unclear. In 3D organotypic coculture with mouse keratinocytes and fibroblasts, the thickness of stratified cell layers was prolonged, and growth arrest and terminal differentiation were delayed when PKCη-null keratinocytes were used. Re-expression of PKCη in PKCη-null keratinocytes restored stratified cell layer thickness, growth arrest and terminal differentiation. We show that in 3D cocultured PKCη-null keratinocytes, p27Kip1 mRNA was downregulated, whereas JNK/c-Jun signaling was enhanced. Furthermore, inhibition of JNK/c-Jun signaling in PKCη-null keratinocytes led to upregulation of p27Kip1 mRNA, and to thinner stratified cell layers. Collectively, our findings indicate that PKCη upregulates p27Kip1 mRNA through suppression of JNK/c-Jun signaling. This results in promoting a proliferation to differentiation switch in keratinocytes.Keywords
This publication has 43 references indexed in Scilit:
- AP1 factor inactivation in the suprabasal epidermis causes increased epidermal hyperproliferation and hyperkeratosis but reduced carcinogen-dependent tumor formationOncogene, 2010
- Mitogenic Regulation of p271 Gene Is Mediated by AP-1 Transcription FactorsPublished by Elsevier BV ,2010
- The tumor suppressor activity of IKKα in stratified epithelia is exerted in part via the TGF-β antiproliferative pathwayProceedings of the National Academy of Sciences, 2008
- CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor DevelopmentThe American Journal of Pathology, 2008
- Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1The Journal of cell biology, 2006
- CDK4 regulation by TNFR1 and JNK is required for NF-κB–mediated epidermal growth controlThe Journal of cell biology, 2005
- Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-IJournal of Cell Science, 2004
- Getting under the skin of epidermal morphogenesisNature Reviews Genetics, 2002
- Differentiation-Associated Localization of nPKCμ, a Ca++-Independent Protein Kinase C, in Normal Human Skin and Skin DiseasesJournal of Investigative Dermatology, 1993
- Changes in Keratinocyte Maturation During Wound HealingJournal of Investigative Dermatology, 1987