Journal
CANCER CELL
Volume 26, Issue 1, Pages 106-120Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2014.05.015
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Funding
- National Science Foundation of China [31270828, 31070678]
- Ministry of Science and Technology, China [2012CB910800, 2013CB910900, 2010CB912101, 2011CB915501]
- NIH [GM095526]
- Sanofi-aventis SIBS Young Investigator award
- Cancer Center of Xuhui Central Hospital [CCR2012003]
- Shanghai Institute of Neurosciences [SKLN-201206]
- Instrument Developing Project of the Chinese Academy of Sciences [YZ201339]
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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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