RRC ID 2416
Author Mariño G, Salvador-Montoliu N, Fueyo A, Knecht E, Mizushima N, López-Otín C.
Title Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3.
Journal J. Biol. Chem.
Abstract Atg4C/autophagin-3 is a member of a family of cysteine proteinases proposed to be involved in the processing and delipidation of the mammalian orthologues of yeast Atg8, an essential component of an ubiquitin-like modification system required for execution of autophagy. To date, the in vivo role of the different members of this family of proteinases remains unclear. To gain further insights into the functional relevance of Atg4 orthologues, we have generated mutant mice deficient in Atg4C/autophagin-3. These mice are viable and fertile and do not display any obvious abnormalities, indicating that they are able to develop the autophagic response required during the early neonatal period. However, Atg4C-/--starved mice show a decreased autophagic activity in the diaphragm as assessed by immunoblotting studies and by fluorescence microscopic analysis of samples from Atg4C-/- GFP-LC3 transgenic mice. In addition, animals deficient in Atg4C show an increased susceptibility to develop fibrosarcomas induced by chemical carcinogens. Based on these results, we propose that Atg4C is not essential for autophagy development under normal conditions but is required for a proper autophagic response under stressful conditions such as prolonged starvation. We also propose that this enzyme could play an in vivo role in events associated with tumor progression.
Volume 282(25)
Pages 18573-83
Published 2007-6-22
DOI 10.1074/jbc.M701194200
PII M701194200
PMID 17442669
MeSH Animals Autophagy* Autophagy-Related Proteins Cysteine Endopeptidases / genetics* Cysteine Endopeptidases / physiology* Disease Models, Animal Disease Progression Female Fibroblasts / metabolism Genetic Vectors Male Mice Mice, Transgenic Models, Genetic Neoplasms / genetics* Time Factors Tissue Distribution
IF 4.106
Times Cited 240