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Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy
Open accessAbstract
Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.
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“UBQLN2 can also act as an autophagy receptor by directly interacting with LC3 in autophagosomes [219,220].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [220]
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Metadata
- Authors
- Rothenberg, C., Srinivasan, D., Mah, L., Kaushik, S., Peterhoff, C. M., Ugolino, J., Fang, S., Cuervo, A. M., Nixon, R. A., & Monteiro, M. J.
- Affiliations
- University of Maryland, Baltimore (US)
- Albert Einstein College of Medicine (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Monteiro, M. J.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-06-07
- Volume
- 19
- Issue
- 16
- Pages
- 3219-3232
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC2908472
- OpenAlex
- W2107562621
- Cited by
- 225
- References
- 52
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 16 · 2021: 17 · 2020: 20 · 2019: 13 · 2018: 21 · 2017: 16 · 2016: 13 · 2015: 18 · 2014: 14 · 2013: 21 · 2012: 15
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (T32 grant)
- National Institute on Aging (AG02190, R01AG016839, AG016839, T32AG023475)
- National Institute of General Medical Sciences (GM066287, R01GM066287, GM06696)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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 › Molecular Biology › Heat shock proteins research
- Keywords
- ubiquilin, autophagy, chaperone-mediated autophagy, macroautophagy, autophagosomes, LC3, autophagosome maturation, protein degradation, Alzheimer's disease, huntingtin exon 1, polyglutamine, HeLa cells
- MeSH terms
- Huntingtin Protein, Autophagy-Related Proteins, Animals, Autophagy, Brain, Carrier Proteins, HeLa Cells, Humans, Lysosomes, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Microtubule-Associated Proteins, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Phagosomes, Protein Binding, Transfection, Blotting, Western, Microscopy, Immunoelectron, Cell Cycle Proteins, Molecular Chaperones, Trinucleotide Repeats, RNA Interference, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Mice, Presenilin-2
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