Division of Infectious Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Curr Cancer Drug Targets. 2019;19(6):468-478. doi: 10.2174/1568009618666181016164920.
The multifunctional signaling hub p62 is well recognized as a ubiquitin sensor and a selective autophagy receptor. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 sorts ubiquitinated substrates including p62 itself for lysosome-mediated degradation. p62 plays crucial roles in myriad cellular processes including DNA damage response, aging/senescence, infection and immunity, chronic inflammation, and cancerogenesis, dependent on or independent of autophagy. Targeting p62-mediated autophagy may represent a promising strategy for clinical interventions of different cancers. In this review, we summarize the transcriptional and post-translational regulation of p62, and its mechanistic roles in cancers, with the emphasis on its roles in regulation of DNA damage response and its connection to the cGAS-STING-mediated antitumor immune response, which is promising for cancer vaccine design.
多功能信号枢纽 p62 是一种公认的泛素传感器和选择性自噬受体。作为泛素传感器，p62 通过促进 TRAF6 的泛素化和聚集来促进 NFκB 的激活。作为选择性自噬受体，p62 将包括 p62 自身在内的泛素化底物分拣出来，进行溶酶体介导的降解。p62 在包括 DNA 损伤反应、衰老/衰老、感染和免疫、慢性炎症以及癌症发生在内的多种细胞过程中发挥关键作用，其作用依赖或不依赖于自噬。靶向 p62 介导的自噬可能代表了不同癌症临床干预的一种有前途的策略。在这篇综述中，我们总结了 p62 的转录后和翻译后调节及其在癌症中的机制作用，重点介绍了其在调节 DNA 损伤反应及其与 cGAS-STING 介导的抗肿瘤免疫反应的关系中的作用，这对癌症疫苗设计具有重要意义。
