Tid1, the mammalian homologue of Drosophila tumor suppressor Tid56, mediates macroautophagy by interacting with beclin1-containing autophagy protein complex

Ge Niu, Huan Zhang, Dan Liu, Li Chen, Chandra Belani, Hong Gang Wang, Hua Cheng

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

One of the fundamental functions of molecular chaperone proteins is to selectively conjugate cellular proteins, targeting them directly to lysosome. Some of chaperones, such as the stress-induced Hsp70, also play important roles in autophagosome-forming macroautophagy under various stress conditions. However, the role of their co-chaperones in autophagy regulation has not been well defined. We here show that Tid1, a DnaJ co-chaperone for Hsp70 and the mammalian homologue of the Drosophila tumor suppressor Tid56, is a key mediator of macroautophagy pathway. Ectopic expression of Tid1 induces autophagy by forming LC3+ autophagosome foci, whereas silencing Tid1 leads to drastic impairment of autophagy as induced by nutrient deprivation or rapamycin. In contrast, Hsp70 is dispensable for a role in nutrient deprivation-induced autophagy. The murine Tid1 can be replaced with human Tid1 in murine fibroblast cells for induction of autophagy. We further show that Tid1 increases autophagy flux by interacting with the Beclin1-PI3 kinase class III protein complex in response to autophagy inducing signal and that Tid1 is an essential mediator that connects IκB kinases to the Beclin1-containing autophagy protein complex. Together, these results reveal a crucial role of Tid1 as an evolutionarily conserved and essential mediator of canonical macroautophagy.

Original languageEnglish (US)
Pages (from-to)18102-18110
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number29
DOIs
StatePublished - Jul 17 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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