Assefa Zerihun, Van Laethem An, Garmyn Marjan, Agostinis Patrizia
Department of Molecular Cell Biology, Division of Physiology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Biochim Biophys Acta. 2005 Jul 25;1755(2):90-106. doi: 10.1016/j.bbcan.2005.04.001.
Epidemiological and experimental evidences have established solar ultraviolet (UV) radiation as the leading cause of skin cancers. Specifically, the frequency of non-melanoma skin cancer, one of the malignancies with the most rapidly increasing incidence, is directly related to the total exposure to solar UV light. As part of a general effort to elucidate the components of cellular signal transduction pathways, the mechanisms of cellular responses to UV radiation have received considerable attention over the last few years. These efforts were driven mainly by the conviction that understanding how normal cells respond to extracellular stimuli such as exposure to UV radiation will undoubtedly help in deciphering what goes wrong in a variety of clinical disorders including skin cancers and will assist in the development of novel therapeutic strategies. Studies over the last decade have established that UV radiation induces a bewildering array of signal transduction pathways, some of which could lead to apoptotic cell death. UV-induced cell death by apoptosis is considered to be a natural protective mechanism that removes damaged keratinocytes and circumvents the risk of malignant transformation. In this review, we summarize some of the most important findings regarding the response and role of mitogen-activated protein kinases in UVA and UVB radiation-induced signaling to apoptosis in keratinocytes. We will also briefly discuss what is known about the role of the BCL-2 family of proteins, the emerging role of lysosomal proteases and other important cytosolic signaling proteins in UV-induced apoptosis.
流行病学和实验证据已证实，太阳紫外线（UV）辐射是皮肤癌的主要病因。具体而言，非黑素瘤皮肤癌是发病率增长最为迅速的恶性肿瘤之一，其发病频率与太阳紫外线的总暴露量直接相关。作为阐明细胞信号转导通路组成部分的一项总体工作的一部分，细胞对紫外线辐射反应的机制在过去几年中受到了相当多的关注。这些工作主要是出于这样一种信念，即了解正常细胞如何对细胞外刺激（如紫外线辐射暴露）做出反应，无疑将有助于解读包括皮肤癌在内的各种临床疾病中出现的问题，并有助于开发新的治疗策略。过去十年的研究表明，紫外线辐射可诱导一系列令人眼花缭乱的信号转导通路，其中一些通路可能导致细胞凋亡性死亡。紫外线诱导的细胞凋亡性死亡被认为是一种自然保护机制，可清除受损的角质形成细胞并规避恶性转化的风险。在本综述中，我们总结了一些关于丝裂原活化蛋白激酶在UVA和UVB辐射诱导角质形成细胞凋亡信号传导中的反应和作用的最重要发现。我们还将简要讨论关于BCL-2蛋白家族的作用、溶酶体蛋白酶的新作用以及其他重要的胞质信号蛋白在紫外线诱导的细胞凋亡中已知的情况。
