RRC ID |
2416
|
著者 |
Mariño G, Salvador-Montoliu N, Fueyo A, Knecht E, Mizushima N, López-Otín C.
|
タイトル |
Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3.
|
ジャーナル |
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.
|
巻・号 |
282(25)
|
ページ |
18573-18583
|
公開日 |
2007-6-22
|
DOI |
10.1074/jbc.M701194200
|
PII |
S0021-9258(20)68958-X
|
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 |
4.238
|
引用数 |
307
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
実験動物マウス |
|