Projects per year
Mechanisms of selective autophagy of the ER, known as ER-phagy, require molecular delineation, particularly in vivo. It is unclear how these events control ER proteostasis and cellular health. Here, we identify cell-cycle progression gene 1 (CCPG1), an ER-resident protein with no known physiological role, as a non-canonical cargo receptor that directly binds to core autophagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete motif, to FIP200. These interactions facilitate ER-phagy. The CCPG1 gene is inducible by the unfolded protein response and thus directly links ER stress to ER-phagy. In vivo, CCPG1 protects against ER luminal protein aggregation and consequent unfolded protein response hyperactivation and tissue injury of the exocrine pancreas. Thus, via identification of this autophagy protein, we describe an unexpected molecular mechanism of ER-phagy and provide evidence that this may be physiologically relevant in ER luminal proteostasis.
|Early online date||28 Dec 2017|
|Publication status||Published - 22 Jan 2018|
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- 2 Finished
A new negative regulator of autophagy in cellular and organismal homoeostasis
1/01/16 → 31/12/18
TBK1 KINASE ADDICTION IN KRAS-DEPENDENT NON SMALL LUNG CANCER: THE ROLE OF AUTOPHAGY
1/02/12 → 31/12/18
- Deanery of Molecular, Genetic and Population Health Sciences - Reader
- Edinburgh Cancer Research Centre
Person: Academic: Research Active