Gupta Ishita, Singh Kanika, Varshney Nishant K, Khan Sameena
Structural Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad, India.
Front Cell Dev Biol. 2018 Feb 9;6:11. doi: 10.3389/fcell.2018.00011. eCollection 2018.
Regulatory functions of the ubiquitin-proteasome system (UPS) are exercised mainly by the ubiquitin ligases and deubiquitinating enzymes. Degradation of apoptotic proteins by UPS is central to the maintenance of cell health, and deregulation of this process is associated with several diseases including tumors, neurodegenerative disorders, diabetes, and inflammation. Therefore, it is the view that interrogating protein turnover in cells can offer a strategy for delineating disease-causing mechanistic perturbations and facilitate identification of drug targets. In this review, we are summarizing an overview to elucidate the updated knowledge on the molecular interplay between the apoptosis and UPS pathways. We have condensed around 100 enzymes of UPS machinery from the literature that ubiquitinates or deubiquitinates the apoptotic proteins and regulates the cell fate. We have also provided a detailed insight into how the UPS proteins are able to fine-tune the intrinsic, extrinsic, and p53-mediated apoptotic pathways to regulate cell survival or cell death. This review provides a comprehensive overview of the potential of UPS players as a drug target for cancer and other human disorders.
泛素-蛋白酶体系统（UPS）的调节功能主要由泛素连接酶和去泛素化酶行使。UPS对凋亡蛋白的降解是维持细胞健康的核心，该过程的失调与包括肿瘤、神经退行性疾病、糖尿病和炎症在内的多种疾病相关。因此，有一种观点认为，研究细胞中的蛋白质周转可以为描绘致病机制扰动提供一种策略，并有助于识别药物靶点。在这篇综述中，我们总结了一个概述，以阐明关于凋亡与UPS途径之间分子相互作用的最新知识。我们从文献中汇总了大约100种UPS机制中的酶，这些酶可使凋亡蛋白泛素化或去泛素化，并调节细胞命运。我们还详细介绍了UPS蛋白如何能够微调内在、外在和p53介导的凋亡途径以调节细胞存活或细胞死亡。这篇综述全面概述了UPS相关蛋白作为癌症和其他人类疾病药物靶点的潜力。
