# The Roles of SQSTM1/p62 in Selective Autophagy and Oncogenic Signaling

## TL;DR

This paper reviews how the protein p62 regulates autophagy and its role in cancer development.

## Contribution

The paper provides a comprehensive review of p62's dual role in autophagy and oncogenic signaling.

## Key findings

- p62 acts as a selective autophagy receptor that targets ubiquitinated proteins for degradation.
- Phase separation of p62 is a key regulatory process in autophagy.
- Dysregulated p62-mediated autophagy is linked to cancer progression.

## Abstract

Autophagy is a critical cellular mechanism that regulates the degradation of misfolded and aggregated proteins and non-functional intracellular organelles. Based on the fundamental qualities of the substrates targeted for degradation and the distinct molecular mechanisms involved, autophagy can be classified into three major types: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Sequestosome 1 (SQSTM1)/p62, which functions as a signaling hub integrating nuclear factor kappa B (NF-κB), the mechanistic target of rapamycin complex 1 (mTORC1), and Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2–related factor 2 (NRF2) pathways, serves as a selective macroautophagy/autophagy receptor that binds ubiquitinated cargo proteins and recruits them to the autophagosome for subsequent degradation in the autolysosome. Furthermore, the phase separation of p62 is an important regulatory process in the autophagy mechanism, but recent studies have demonstrated that impaired or excessive autophagy mediated by p62 is associated with cancer development. This review summarizes the role of autophagy—including its types, mechanisms, and the pathway related to the ubiquitin-dependent selective autophagy receptor p62—in cancer progression.