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

Zhengzhao Liu, Peng Chen, Hong Gao, Yu Gu, Jiao Yang, Hong Peng, Xingxing Xu, Haifeng Wang, Meiqiang Yang, Xiaoying Liu, Libin Fan, Shiyao Chen, Jian Zhou, Yihong Sun, Kangchen Ruan, Shuqun Cheng, Masaaki Komatsu, Eileen White, Lin Li, Hongbin JiDaniel Finley, Ronggui Hu

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)106-120
Number of pages15
JournalCancer Cell
Issue number1
StatePublished - Jul 14 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression'. Together they form a unique fingerprint.

Cite this