Univ. Grenoble Alpes, SYMMES/CIBEST UMR 5819 UGA-CNRS-CEA, IRIG/CEA-Grenoble, Grenoble, France.
Univ. Grenoble Alpes, CEA, Inserm, BIG-BGE U1038, 38000 Grenoble, France.
Oxid Med Cell Longev. 2021 Apr 28;2021:6689403. doi: 10.1155/2021/6689403. eCollection 2021.
Xeroderma pigmentosum (XP) is a rare autosomal genodermatosis that manifests clinically with pronounced sensitivity to ultraviolet (UV) radiation and the high probability of the occurrence of different skin cancer types in XP patients. XP is mainly caused by mutations in XP-genes that are involved in the nucleotide excision repair (NER) pathway that functions in the removal of bulky DNA adducts. Besides, the aggregation of DNA lesions is a life-threatening event that might be a key for developing various mutations facilitating cancer appearance. One of the key players of NER is XPC that senses helical distortions found in damaged DNA. The majority of XPC gene mutations are nonsense, and some are missense leading either to the loss of XPC protein or to the expression of a truncated nonfunctional version. Given that no cure is yet available, XPC patients should be completely protected and isolated from all types of UV radiations (UVR). Although it is still poorly understood, the characterization of the proteomic signature of an XPC mutant is essential to identify mediators that could be targeted to prevent cancer development in XPC patients. Unraveling this proteomic signature is fundamental to decipher the signaling pathways affected by the loss of XPC expression following exposure to UVB radiation. In this review, we will focus on the signaling pathways disrupted in skin cancer, pathways modulating NER's function, including XPC, to disclose signaling pathways associated with XPC loss and skin cancer occurrence.
着色性干皮病（XP）是一种罕见的常染色体遗传皮肤病，临床上表现为对紫外线（UV）辐射的敏感性显著增加，XP 患者发生不同类型皮肤癌的概率很高。XP 主要由 XP 基因的突变引起，这些基因参与核苷酸切除修复（NER）途径，该途径在去除大体积 DNA 加合物方面起作用。此外，DNA 损伤的聚集是危及生命的事件，可能是导致各种促进癌症发生的突变的关键。NER 的关键参与者之一是 XPC，它可以感知受损 DNA 中发现的螺旋扭曲。大多数 XPC 基因突变是无义的，有些是错义的，导致 XPC 蛋白的丢失或表达截短的无功能版本。由于目前尚无治愈方法，XPC 患者应完全受到保护，使其与所有类型的紫外线辐射（UVR）隔离。尽管目前还了解甚少，但对 XPC 突变体的蛋白质组特征进行表征对于确定可以作为预防 XPC 患者癌症发展的靶点的介质至关重要。揭示这种蛋白质组特征对于阐明 XPC 表达缺失后暴露于 UVB 辐射所影响的信号通路至关重要。在这篇综述中，我们将重点讨论在皮肤癌中被破坏的信号通路，以及调节 NER 功能的通路，包括 XPC，以揭示与 XPC 缺失和皮肤癌发生相关的信号通路。
