Cancer Cell
Volume 26, Issue 1, 14 July 2014, Pages 106-120
Journal home page for Cancer Cell

Article
Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression

https://doi.org/10.1016/j.ccr.2014.05.015Get rights and content
Under an Elsevier user license
open archive

Highlights

  • HACE1 mediates ubiquitylation of autophagy receptor OPTN in vitro and in vivo

  • HACE1-ubiquitylated OPTN interacts with p62 to form autophagy receptor complex

  • Lys48-linked polyubiquitin chains on OPTN target it for autophagic degradation

  • HACE1 and OPTN constitute an axis to activate autophagy and suppress tumor

Summary

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.

Cited by (0)

12

Co-first author