Post-Translational Modification of p62: Roles and Regulations in Autophagy
Autophagy is a highly conserved cellular process that plays a crucial role in maintaining cellular homeostasis by degrading damaged organelles, misfolded proteins, and other cellular components. p62/SQSTM1 functions as a selective autophagy receptor by binding polyubiquitinated cargo through its UBA...
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2025-07-01
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| author | Shuai Xiao Yeping Yu Meng Liao Dandan Song Xiaozhen Xu Lingli Tian Rui Zhang Hao Lyu Dong Guo Qi Zhang Xing-Zhen Chen Cefan Zhou Jingfeng Tang |
| author_facet | Shuai Xiao Yeping Yu Meng Liao Dandan Song Xiaozhen Xu Lingli Tian Rui Zhang Hao Lyu Dong Guo Qi Zhang Xing-Zhen Chen Cefan Zhou Jingfeng Tang |
| author_sort | Shuai Xiao |
| collection | DOAJ |
| description | Autophagy is a highly conserved cellular process that plays a crucial role in maintaining cellular homeostasis by degrading damaged organelles, misfolded proteins, and other cellular components. p62/SQSTM1 functions as a selective autophagy receptor by binding polyubiquitinated cargo through its UBA domain and linking it to microtubule-associated protein light chain 3 (LC3)-decorated autophagosomes. Moreover, p62 acts as a signaling hub and is essential in response to various stressors, including nutrient deprivation and oxidative stress. Post-translational modifications (PTMs) critically regulate p62’s multifaceted roles, controlling p62’s phase separation, cargo recruitment, signaling interactions, and autophagic degradation efficiency. The dysregulation of p62 PTMs is closely related to the occurrence and development of human diseases, particularly neurodegenerative disorders and certain cancers. This review summarizes the main PTM events of p62 discovered to date that influence the autophagy process, including phosphorylation, acetylation, ubiquitination, and S-acylation, as well as their known contributions to protein aggregation and disease. The PTMs of p62 dynamically regulate autophagy, protein aggregation, and cellular signaling, underscoring its importance as a potential therapeutic target and biomarker for these diseases. |
| format | Article |
| id | doaj-art-ca3a802232884de9a7bfb3e2c9be7f9e |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-ca3a802232884de9a7bfb3e2c9be7f9e2025-08-20T03:16:55ZengMDPI AGCells2073-44092025-07-011413101610.3390/cells14131016Post-Translational Modification of p62: Roles and Regulations in AutophagyShuai Xiao0Yeping Yu1Meng Liao2Dandan Song3Xiaozhen Xu4Lingli Tian5Rui Zhang6Hao Lyu7Dong Guo8Qi Zhang9Xing-Zhen Chen10Cefan Zhou11Jingfeng Tang12National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaMembrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, CanadaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaNational “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, ChinaAutophagy is a highly conserved cellular process that plays a crucial role in maintaining cellular homeostasis by degrading damaged organelles, misfolded proteins, and other cellular components. p62/SQSTM1 functions as a selective autophagy receptor by binding polyubiquitinated cargo through its UBA domain and linking it to microtubule-associated protein light chain 3 (LC3)-decorated autophagosomes. Moreover, p62 acts as a signaling hub and is essential in response to various stressors, including nutrient deprivation and oxidative stress. Post-translational modifications (PTMs) critically regulate p62’s multifaceted roles, controlling p62’s phase separation, cargo recruitment, signaling interactions, and autophagic degradation efficiency. The dysregulation of p62 PTMs is closely related to the occurrence and development of human diseases, particularly neurodegenerative disorders and certain cancers. This review summarizes the main PTM events of p62 discovered to date that influence the autophagy process, including phosphorylation, acetylation, ubiquitination, and S-acylation, as well as their known contributions to protein aggregation and disease. The PTMs of p62 dynamically regulate autophagy, protein aggregation, and cellular signaling, underscoring its importance as a potential therapeutic target and biomarker for these diseases.https://www.mdpi.com/2073-4409/14/13/1016post-translational modificationsautophagyp62oligomerization |
| spellingShingle | Shuai Xiao Yeping Yu Meng Liao Dandan Song Xiaozhen Xu Lingli Tian Rui Zhang Hao Lyu Dong Guo Qi Zhang Xing-Zhen Chen Cefan Zhou Jingfeng Tang Post-Translational Modification of p62: Roles and Regulations in Autophagy Cells post-translational modifications autophagy p62 oligomerization |
| title | Post-Translational Modification of p62: Roles and Regulations in Autophagy |
| title_full | Post-Translational Modification of p62: Roles and Regulations in Autophagy |
| title_fullStr | Post-Translational Modification of p62: Roles and Regulations in Autophagy |
| title_full_unstemmed | Post-Translational Modification of p62: Roles and Regulations in Autophagy |
| title_short | Post-Translational Modification of p62: Roles and Regulations in Autophagy |
| title_sort | post translational modification of p62 roles and regulations in autophagy |
| topic | post-translational modifications autophagy p62 oligomerization |
| url | https://www.mdpi.com/2073-4409/14/13/1016 |
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