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Structure of the Human Autophagy Initiating Kinase ULK1 in Complex with Potent Inhibitors
Abstract
Autophagy is a conserved cellular process that involves the degradation of cellular components for energy maintenance and cytoplasmic quality control that has recently gained interest as a novel target for a variety of human diseases, including cancer. A prime candidate to determine the potential therapeutic benefit of targeting autophagy is the kinase ULK1, whose activation initiates autophagy. Here, we report the first structures of ULK1, in complex with multiple potent inhibitors. These structures show features unique to the enzyme and will provide a path for the rational design of selective compounds as cellular probes and potential therapeutics.
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ULK1 autophosphorylates and transphosphorylates its binding partners ATG13, RB1CC1, and ATG101.
“that ULK1 autophosphorylates and transphosphorylates its binding partners ATG13, RB1CC1, and ATG101 [644, 645, 692-700].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [696]
Plate assays for monitoring the activity of peroxisomal oxidases in yeast colonies are available.
“Plate assays for monitoring the activity of peroxisomal oxidases in yeast colonies are also available [690,696].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [696]
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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
The mammalian ULK1 complex and autophagy initiation
Zachari, M., & Ganley, I. G. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170021 · Cited by 789
Pasquier, B. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2104-y · Cited by 329
Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19
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Metadata
- Authors
- Lazarus, M. B., Novotny, C. J., & Shokat, K. M.
- Affiliations
- University of California, San Francisco , , , ,
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-12-31
- Volume
- 10
- Issue
- 1
- Pages
- 257-261
- ISSN
- 1554-8929
- 1554-8937
- PMC
- PMC4301081
- Cited by
- 154
- References
- 6
- Language
- en
- Funders
- Howard Hughes Medical Institute (NA)
- National Institute of Allergy and Infectious Diseases (R01 AI094098)
- Helen Hay Whitney Foundation (NA)
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