Related Experiment Video
Updated: Feb 10, 2026
Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry
Published on: July 21, 2017
Autophagic Regulation of p62 is Critical for Cancer Therapy
Md Ariful Islam1, Mopa Alina Sooro2, Pinghu Zhang3
1Jiangsu Key Laboratory of New Drug Screening & Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. ariful.islam1107@gmail.com.
Abstract:
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.
Insights
Sequestosome1 (p62) is a key protein in autophagy and apoptosis. Its dysregulation is linked to cancer, highlighting its potential as a therapeutic target.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Sequestosome1 (p62) is a multidomain protein crucial for autophagy, acting as an adaptor for cargo recognition and sequestration.
- p62 interacts with LC3 via its LIR domain and ubiquitinated proteins via its UBA domain, facilitating cargo delivery to autophagosomes.
- The PB1 domain of p62 mediates the formation of inclusion bodies, sequestering target cargo.
Purpose of the Study:
- To review the multifaceted role of p62 in autophagy and apoptosis.
- To elucidate how p62's distinct domains contribute to its functions in cellular processes.
- To discuss the implications of p62 dysregulation in cancer development and therapy resistance.
Main Methods:
- Literature review of studies investigating p62's function in autophagy and apoptosis.
- Analysis of research linking p62 to oncogenic transformations and cancer progression.
- Examination of the role of p62 domains in protein interactions and cellular signaling.
Main Results:
- p62 acts as a central hub, interacting with autophagy machinery and signaling proteins.
- Upregulation or reduced degradation of p62 is associated with tumor formation, cancer promotion, and therapeutic resistance.
- Emerging evidence points to autophagy-dependent apoptotic activity of p62.
Conclusions:
- p62 plays a critical role in both autophagy and apoptosis.
- Modulating cellular p62 levels presents a promising strategy for cancer therapeutics.
- Understanding p62's domain-specific functions is key to developing targeted cancer treatments.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
01:16Critical Region, Critical Values and Significance Level
In hypothesis testing, a sample statistic is converted to a test statistic using z, t, or chi-square distribution. A critical region is an area under the curve in probability distributions demarcated by the critical value. When the test statistic falls in this region, it suggests that the null hypothesis must be rejected. As this region contains all those values of the...