Bak在紫外线诱导的皮肤癌细胞凋亡中的作用及人乳头瘤病毒E6蛋白对其的消除作用
Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins.
作者信息
Jackson S, Harwood C, Thomas M, Banks L, Storey A
机构信息
Imperial Cancer Research Fund, Skin Tumour Laboratory, Centre for Cutaneous Research, London E1 2AT, UK.
出版信息
Genes Dev. 2000 Dec 1;14(23):3065-73. doi: 10.1101/gad.182100.
Abstract
Ultraviolet B (UVB) damage is recognized as the most important etiological factor in the development of skin cancer. Human papillomaviruses (HPV) have also been implicated in the disease, although the mechanism of action of these viruses remains unknown. We present evidence here that Bak protein is involved in signaling apoptosis in the skin in response to UVB damage, and that cutaneous HPV E6 proteins target and abrogate Bak function by promoting its proteolytic degradation both in vitro and in regenerated epithelium. Additionally, HPV positive skin cancers had undetectable levels of Bak in contrast to HPV negative cancers, which expressed Bak. This study supports a link between the virus and UVB in the induction of HPV-associated skin cancer and reveals a survival mechanism of virally infected cells.
摘要
紫外线B（UVB）损伤被认为是皮肤癌发生发展中最重要的病因。人乳头瘤病毒（HPV）也与该疾病有关，尽管这些病毒的作用机制尚不清楚。我们在此提供证据表明，Bak蛋白参与皮肤对UVB损伤的凋亡信号传导，并且皮肤HPV E6蛋白通过在体外和再生上皮中促进其蛋白水解降解来靶向并消除Bak功能。此外，与表达Bak的HPV阴性癌症相比，HPV阳性皮肤癌中检测不到Bak水平。这项研究支持了病毒与UVB在诱导HPV相关皮肤癌中的联系，并揭示了病毒感染细胞的存活机制。
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