ArticleCell death & disease2022
Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Review
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- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Immunoproteasome remodeling in senescing human macrophages reveals the loss of PA28αβ capping as a hallmark of immunosenescence.Communications biology · 2025Article
- LncRNA DEPDC1-AS1 drives the progression of endometrial carcinoma by regulating miR-508-3p.Discover oncology · 2025Article
- Aging and diet alter the protein ubiquitylation landscape in the mouse brain.Nature communications · 2025Article
- A positive feedback loop of OTUD1 and c-Jun driven by leptin expedites stemness maintenance in ovarian cancer.Oncogene · 2025Article
- Delineating cysteine-reactive compound modulation of cellular proteostasis processes.Nature chemical biology · 2025Article
- Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway.Journal of endocrinological investigation · 2025Article
- Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.Cell biology and toxicology · 2025Article
- The aggrephagy-related gene TUBA1B influences clinical outcomes in glioma patients by regulating the cell cycle.Frontiers in oncology · 2025Article
- CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction.EMBO reports · 2024Article
- Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.Communications biology · 2024Article
- A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- ALKBH1 promotes HIF-1α-mediated glycolysis by inhibiting N-glycosylation of LAMP2A.Cellular and molecular life sciences : CMLS · 2024Article
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
- Inhibition of SQSTM1 S403 phosphorylation facilitates the aggresome formation of ubiquitinated proteins during proteasome dysfunction.Cellular & molecular biology letters · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggresome formation is a protective cellular response to counteract proteasome dysfunction by sequestering misfolded proteins and reducing proteotoxic stress. Autophagic degradation of the protein aggregates is considered to be a key compensating mechanism for balancing proteostasis. However, the precise role of autophagy in proteasome inhibition-induced aggresome biogenesis remains unclear. Herein, we demonstrate that in the early stage of proteasome inhibition, the maturation of the autophagosome is suppressed, which facilitates aggresome formation of misfolded proteins. Proteasome inhibition-induced phosphorylation of SQSTM1 T269/S272 inhibits its autophagic receptor activity and promotes aggresome formation of misfolded proteins. Inhibiting SQSTM1 T269/S272 phosphorylation using Doramapimod aggravates proteasome inhibitor-mediated cell damage and tumor suppression. Taken together, our data reveal a negative effect of autophagy on aggresome biogenesis and cell damage upon proteasome inhibition. Our study suggests a novel therapeutic intervention for proteasome inhibitor-mediated tumor treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.