Perspective
Journal of Investigative Dermatology (2006) 126, 243–257. doi:10.1038/sj.jid.5700008
Keratinocyte Apoptosis in Epidermal Development and Disease
Deepak Raj1,2, Douglas E Brash3,4 and Douglas Grossman1,2,5
- 1Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
- 2Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
- 3Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA
- 4Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA
- 5Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA
Correspondence: Douglas Grossman, Huntsman Cancer Institute, Suite 5243, 2000 Circle of Hope, Salt Lake City, Utah 84112, USA. Email: doug.grossman@hci.utah.edu
Received 5 July 2005; Revised 16 August 2005; Accepted 2 September 2005.
Abstract
Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal development and restraining carcinogenesis. Apoptosis balances proliferation to maintain epidermal thickness, contributes to stratum corneum formation and may eliminate pre-malignant cells. Apart from the normal developmental program, KC apoptosis can be triggered by UV light and other stimuli. Dysfunctional apoptosis occurs in some skin diseases, such as psoriasis and skin cancer. Here we review the current state of knowledge of KC apoptosis, with particular focus on apoptotic signaling pathways and molecular mechanisms of apoptosis control, and discuss new insights into the complex role of apoptosis in skin carcinogenesis that are emerging from mouse models.
Abbreviations:
ASK1, apoptosis signal-regulating kinase-1; ced, Caenorhabditis elegans death; DLK, dual leucine zipper-bearing kinase; EGF, epidermal growth factor; ERK, extracellular signal-regulated kinase; Fas-L, Fas ligand; IAP, inhibitor of apoptosis (gene family); KC, keratinocyte; MAPK, mitogen-activated protein kinase; SCC, squamous-cell carcinoma; TNF, tumor necrosis factor
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