The RUN Domain of Rubicon Is Important for hVps34 Binding, Lipid Kinase Inhibition, and Autophagy Suppression
Open accessAbstract
The class III phosphatidylinositol 3-kinase (PI3KC3) plays a central role in autophagy. Rubicon, a RUN domain-containing protein, is newly identified as a PI3KC3 subunit through its association with Beclin 1. Rubicon serves as a negative regulator of PI3KC3 and autophagosome maturation. The molecular mechanism underlying the PI3KC3 and autophagy inhibition by Rubicon is largely unknown. Here, we demonstrate that Rubicon interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain. The RUN domain contributes to the efficient inhibition of PI3KC3 lipid kinase activity by Rubicon. Furthermore, a Rubicon RUN domain deletion mutant fails to complement the autophagy deficiency in Rubicon-depleted cells. Hence, these results reveal a critical role of the Rubicon RUN domain in PI3KC3 and autophagy regulation.
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RUBCN is an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.
“Interestingly, while RUBCN is a LAP-specific mediator, it is also an inhibitor of autophagy, localizing to late endosomes/lysosomes to inhibit autophagosome maturation.21,22”
From RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye (2017) · cites this paper as [21]
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References 27 · Cited by 153
Research works printed but not linked: 2
- Sun, Q., Fan, W., Chen, K., Ding, X., Chen, S., and Zhong, Q. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 19211-19216
- Sun, Q., Westphal, W., Wong, K. N., Tan, I., and Zhong, Q. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 19338 -19343
- Authors
- Sun, Q., Zhang, J., Fan, W., Wong, K. N., Ding, X., Chen, S., & Zhong, Q.
- Affiliations
- University of California, Berkeley (US)
- National Institute of Biological Sciences, Beijing (CN)
- Corresponding author
- Zhong, Qing
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 286
- Issue
- 1
- Pages
- 185-191
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3012973
- OpenAlex
- W2053981201
- Cited by
- 153
- References
- 27
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 5 · 2012: 7
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Cancer Institute (R01CA133228)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- Rubicon, class III phosphatidylinositol 3-kinase, autophagy regulation, autophagosome maturation, Beclin-1, protein-protein interaction
- MeSH terms
- Autophagy-Related Proteins, Autophagy, Humans, Protein Binding, Protein Structure, Tertiary, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, HEK293 Cells, Class III Phosphatidylinositol 3-Kinases
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