Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Japan.
Department of Physiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
FEBS J. 2019 Jan;286(1):8-23. doi: 10.1111/febs.14712. Epub 2018 Dec 18.
p62 is a stress-inducible protein able to change among binding partners, cellular localizations and form liquid droplet structures in a context-dependent manner. This protein is mainly defined as a cargo receptor for selective autophagy, a process that allows the degradation of detrimental and unnecessary components through the lysosome. Besides this role, its ability to interact with multiple binding partners allows p62 to act as a main regulator of the activation of the Nrf2, mTORC1, and NF-κB signaling pathways, linking p62 to the oxidative defense system, nutrient sensing, and inflammation, respectively. In the present review, we will present the molecular mechanisms behind the control p62 exerts over these pathways, their interconnection and how their deregulation contributes to cancer progression.
p62 是一种应激诱导蛋白,能够在不同的结合伴侣、细胞定位和形成液滴结构之间转换,这种转换依赖于上下文。这种蛋白质主要被定义为选择性自噬的货物受体,这是一种通过溶酶体降解有害和不必要成分的过程。除了这个作用,它与多个结合伴侣相互作用的能力使 p62 能够作为 Nrf2、mTORC1 和 NF-κB 信号通路激活的主要调节剂,分别将 p62 与氧化防御系统、营养感应和炎症联系起来。在本综述中,我们将介绍 p62 对这些通路的调控背后的分子机制,以及它们之间的相互联系和它们的失调如何促进癌症的进展。