Autophagic Regulation of p62 is Critical for Cancer Therapy

International Journal of Molecular Sciences

Pinghu Zhang¹  Md.Ariful Islam²  MopaAlina Sooro² 

[1] Institute of Translational Medicine & Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China;Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China;

关键词: p62;    PB1;    self-oligomerization;    autophagy;    apoptosis;    cancer;    therapy;   

DOI  :  10.3390/ijms19051405

来源: DOAJ

【 摘 要 】

Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting (LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain. This protein is further the central hub that interacts with several key signaling proteins. Emerging evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed, p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer promotion as well as in resistance to therapy. It has been established that the process of autophagy regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported. It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and outline the importance of modulating cellular levels of p62 in cancer therapeutics.

【 授权许可】

Unknown