p62 links the autophagy pathway and the ubiqutin–proteasome system upon ubiquitinated protein degradation

Cellular & Molecular Biology Letters

Lin Ye¹  Lin Jie Guo¹  Wei Fang Huang¹  Chen Yang¹  Hua Feng Liu¹  Wei Jing Liu²  Zi Gan Xu¹  Hong Luan Wu¹ 

[1] The Institute of Nephrology, Guangdong Medical University, Zhanjiang, China$$;The Institute of Nephrology, Guangdong Medical University, Zhanjiang, China$$Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China$$

关键词: p62;    Autophagy;    Ubiquitin–proteasome system (UPS);    Ubiquitinated protein;    Aggresome;    Proteostasis;    p62 phosphorylation;    Keap1–Nrf2 pathway;    Histone deacetylase 6 (HDAC6);    Mechanistic target of rapamycin complex 1 (mTORC1);   

DOI  :  10.1186/s11658-016-0031-z

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

The ubiquitin–proteasome system (UPS) and autophagy are two distinct and interacting proteolytic systems. They play critical roles in cell survival under normal conditions and during stress. An increasing body of evidence indicates that ubiquitinated cargoes are important markers of degradation. p62, a classical receptor of autophagy, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1–Nrf2 pathway. It is involved in the proteasomal degradation of ubiquitinated proteins. When the cellular p62 level is manipulated, the quantity and location pattern of ubiquitinated proteins change with a considerable impact on cell survival. Altered p62 levels can even lead to some diseases. The proteotoxic stress imposed by proteasome inhibition can activate autophagy through p62 phosphorylation. A deficiency in autophagy may compromise the ubiquitin–proteasome system, since overabundant p62 delays delivery of the proteasomal substrate to the proteasome despite proteasomal catalytic activity being unchanged. In addition, p62 and the proteasome can modulate the activity of HDAC6 deacetylase, thus influencing the autophagic degradation.

【 授权许可】

Unknown