Autophagic Regulation of p62 is Critical for Cancer Therapy.

Autophagic Regulation of p62 is Critical for Cancer Therapy.
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DOI:
10.3390/ijms19051405
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发表时间:
2018-05-08
影响因子:
5.6
通讯作者:
Zhang P
Zhang P
中科院分区:
生物学2区
文献类型:
--
作者:
Islam MA;Sooro MA;Zhang P

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Sequestosome1(p62/SQSTM 1)是一种与自噬机制相互作用的多域蛋白,是靶向货物的关键接头。它通过LC3相互作用结构域(LIR)与吞噬分子相互作用,并通过泛素相关结构域(UBA)与泛素蛋白聚集体相互作用。它通过其PB1结构域将目标货物隔离到包涵体中。该蛋白进一步是与几个关键信号蛋白相互作用的中心枢纽。新出现的证据表明,p62参与了多种细胞致癌转化的诱导。事实上,p62表达上调和/或降解减少与肿瘤的形成、癌症的促进以及对治疗的抵抗有关。现已证实,自噬过程调节p62的水平。最近有报道称p62的自噬依赖于细胞的凋亡活性。很明显,p62在自噬和细胞凋亡中都起着关键作用。因此,在这篇综述中,我们从p62的不同区域讨论了p62在自噬、细胞凋亡和癌症中的作用,并概述了调控细胞水平在癌症治疗中的重要性。
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.
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