Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression
Open accessAbstract
In selective autophagy, receptors are central for cargo selection and delivery. However, it remains yet unclear whether and how multiple autophagy receptors might form complex and function concertedly to control autophagy. Optineurin (OPTN), implicated genetically in glaucoma and amyotrophic lateral sclerosis, was a recently identified autophagy receptor. Here we report that tumor-suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux. Interestingly, the Lys48-linked polyubiquitin chains that HACE1 conjugates onto OPTN might predominantly target OPTN for autophagic degradation. By demonstrating that the HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells, our findings may open an avenue for developing autophagy-targeted therapeutic intervention into cancer.
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OPTN directly interacts with SQSTM1 to form an autophagy receptor complex that accelerates autophagy flux.
“OPTN also directly interacts with SQSTM1 to form an autophagy receptor complex that accelerates autophagy flux [257].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [257]
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References 50 · Cited by 254
- Authors
- Liu, Z., Chen, P., Gao, H., Gu, Y., Yang, J., Peng, H., Xu, X., Wang, H., Yang, M., Liu, X., Fan, L., Chen, S., Zhou, J., Sun, Y., Ruan, K., Cheng, S., Komatsu, M., White, E., Li, L., Ji, H., Finley, D., & Hu, R.
- Affiliations
- Chinese Academy of Sciences (CN)
- Shanghai Medical College of Fudan University (CN)
- Anhui Medical University (CN)
- Fudan University (CN)
- Second Military Medical University (CN)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Rutgers, The State University of New Jersey (US)
- Harvard University (US)
- Corresponding author
- Hu, Ronggui
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 26
- Issue
- 1
- Pages
- 106-120
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4166492
- OpenAlex
- W2005757378
- Cited by
- 254
- References
- 50
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 24 · 2023: 18 · 2022: 14 · 2021: 27 · 2020: 34 · 2019: 29 · 2018: 23 · 2017: 24 · 2016: 16 · 2015: 12 · 2014: 1
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Sanofi
- National Natural Science Foundation of China (2012CB910800, 31270828, 201206, 31070678, 2013CB910900)
- Chinese Academy of Sciences (2013CB910900, 2012CB910800, YZ201339)
- Shanghai Xuhui District Central Hospital
- National Institutes of Health
- National Cancer Institute (R01CA130893, R01CA163591)
- National Institute of General Medical Sciences (R01GM095526)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- optineurin, HACE1, selective autophagy, autophagy receptors, ubiquitination, p62, autophagic flux, tumor suppression, lung cancer, autophagy-targeted therapy
- MeSH terms
- Sequestosome-1 Protein, Animals, Autophagy, DNA Damage, Eye Proteins, Heat-Shock Proteins, Humans, Lung Neoplasms, Lysine, Macrophages, Mice, Inbred C57BL, Mice, Nude, Microtubule-Associated Proteins, Protein Binding, Time Factors, Transfection, Signal Transduction, Mice, Knockout, Oxidative Stress, Cell Cycle Proteins, Tumor Suppressor Proteins, Membrane Transport Proteins, RNA Interference, Transcription Factor TFIIIA, Ubiquitin-Protein Ligases, Cell Line, Tumor, Tumor Burden, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, Ubiquitination, HEK293 Cells
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