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FEBS J. 2022 Jan 07; doi: 10.1111/febs.16345. Epub 2022 Jan 07.

Off-target inhibition of NGLY1 by the poly-caspase inhibitor Z-VAD-fmk induces cellular autophagy.

The FEBS journal

Sarah H Needs, Martin D Bootman, Jeff E Grotzke, Holger B Kramer, Sarah A Allman

Affiliations

  1. School of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
  2. School of Pharmacy, University of Reading, Reading, RG6 6DZ, UK.
  3. Yale University School of Medicine, New Haven, CT, 06520, USA.
  4. Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
  5. MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
  6. Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.

PMID: 34995415 DOI: 10.1111/febs.16345

Abstract

The pan-caspase inhibitor Z-VAD-fmk acts as an inhibitor of peptide:N-glycanase (NGLY1); an endoglycosidase which cleaves N-linked glycans from glycoproteins exported from the endoplasmic reticulum (ER) during ER-associated degradation (ERAD). Both pharmacological N-glycanase inhibition by Z-VAD-fmk and siRNA-mediated knockdown (KD) of NGLY1 induce GFP-LC3 positive puncta in HEK 293 cells. Activation of ER stress markers or induction of reactive oxygen species (ROS) are not observed under either condition. Moreover, Ca

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Keywords: NGLY1; Peptide:N-glycanase 1; Z-VAD-fmk; autophagosome proteomics; autophagy

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