Fas ligand: a sensor for DNA damage critical in skin cancer etiology.

Abstract

DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed "cellular proofreading." Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis. Thus, FasL-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.

• Authors: L L Hill, A Ouhtit, S M Loughlin, M L Kripke, H N Ananthaswamy, L B Owen-Schaub
• Journal: Science (New York, N.Y.) (Science) Vol. 285 Issue 5429 Pg. 898-900 (Aug 06 1999) ISSN: 0036-8075 [Print] United States
• PMID: 10436160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fas Ligand Protein
• Fasl protein, mouse
• Membrane Glycoproteins
• fas Receptor

Topics

• Animals
• Apoptosis
• DNA Damage
• Epidermal Cells
• Epidermis (metabolism, radiation effects)
• Fas Ligand Protein
• Genes, p53
• Keratinocytes (cytology, metabolism, radiation effects)
• Membrane Glycoproteins (genetics, physiology)
• Mice
• Mice, Inbred C3H
• Mutation
• Skin Neoplasms (etiology, pathology)
• Ultraviolet Rays
• Up-Regulation
• fas Receptor (genetics, physiology)