University of Bordeaux, INSERM U1035, BMGIC, Bordeaux, France; PRASE, Lebanese University, Beirut, Lebanon.
PRASE, Lebanese University, Beirut, Lebanon.
Mutat Res Rev Mutat Res. 2022 Jan-Jun;789:108400. doi: 10.1016/j.mrrev.2021.108400. Epub 2021 Nov 20.
Xeroderma pigmentosum group C protein (XPC) acts as a DNA damage recognition factor for bulky adducts and as an initiator of global genome nucleotide excision repair (GG-NER). Novel insights have shown that the role of XPC is not limited to NER, but is also implicated in DNA damage response (DDR), as well as in cell fate decisions upon stress. Moreover, XPC has a proteolytic role through its interaction with p53 and casp-2S. XPC is also able to determine cellular outcomes through its interaction with downstream proteins, such as p21, ARF, and p16. XPC interactions with effector proteins may drive cells to various fates such as apoptosis, senescence, or tumorigenesis. In this review, we explore XPC's involvement in different molecular pathways in the cell and suggest that XPC can be considered not only as a genomic caretaker and gatekeeper but also as a tumor suppressor and cellular-fate decision maker. These findings envisage that resistance to cell death, induced by DNA-damaging therapeutics, in highly prevalent P53-deficent tumors might be overcome through new therapeutic approaches that aim to activate XPC in these tumors. Moreover, this review encourages care providers to consider XPC status in cancer patients before chemotherapy in order to improve the chances of successful treatment and enhance patients' survival.
着色性干皮病组 C 蛋白（XPC）作为一种 DNA 损伤识别因子，可识别大体积加合物，并作为全基因组核苷酸切除修复（GG-NER）的启动子。新的研究结果表明，XPC 的作用不仅限于 NER，还与 DNA 损伤反应（DDR）以及应激时的细胞命运决定有关。此外，XPC 通过与 p53 和 casp-2S 的相互作用发挥蛋白水解作用。XPC 还可以通过与下游蛋白（如 p21、ARF 和 p16）相互作用来决定细胞的命运。XPC 与效应蛋白的相互作用可能使细胞走向不同的命运，如凋亡、衰老或肿瘤发生。在这篇综述中，我们探讨了 XPC 在细胞中不同分子途径中的作用，并提出 XPC 不仅可以被视为基因组的守护者和守门员，还可以被视为肿瘤抑制因子和细胞命运决定因子。这些发现表明，通过旨在激活这些肿瘤中 XPC 的新治疗方法，可能克服由 DNA 损伤治疗药物引起的对细胞死亡的耐药性。此外，这篇综述鼓励医疗保健提供者在癌症患者接受化疗前考虑 XPC 状态，以提高成功治疗的机会并提高患者的生存率。
