RETRACTED: Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy (Retracted article. See vol. 294, pg. 1431, 2019)

被引:178
作者
Mariño, G
Uría, JA
Puente, XS
Quesada, V
Bordallo, J
López-Otín, C
机构
[1] Univ Oviedo, Dept Bioquim & Biol Mol, Fac Med, Inst Univ Oncol, E-33006 Oviedo, Spain
[2] Univ Oviedo, Area Farmacol, Fac Med, Inst Univ Oncol, E-33006 Oviedo, Spain
关键词
D O I
10.1074/jbc.M208247200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have cloned four human cDNAs encoding putative cysteine proteinases that have been tentatively called autophagins. These proteins are similar to Apg4/Aut2, a yeast enzyme involved in the activation of Apg8/Aut7 during the process of autophagy. The identified proteins ranging in length from 393 to 474 amino acids also contain several structural features characteristic of cysteine proteinases including a conserved cysteine residue that is essential for the catalytic properties of these enzymes. Northern blot analysis demonstrated that autophagins are broadly distributed in human tissues, being especially abundant in skeletal muscle. Functional and morphological analysis in autophagy-defective yeast strains lacking Apg4/Aut2 revealed that human autophagins-1 and -3 were able to complement the deficiency in the yeast protease, restoring the phenotypic and biochemical characteristics of autophagic cells. Enzymatic studies performed with autophagin-3, the most widely expressed human autophagin, revealed that the recombinant protein hydrolyzed the synthetic substrate Mca-Thr-Phe-Gly-Met-Dpa-NH2 whose sequence derives from that present around the Apg4 cleavage site in yeast ApgB/Aut7. This proteolytic activity was diminished by N-ethylmaleimide, an inhibitor of cysteine proteases including yeast Apg4/Aut2. These results provide additional evidence that the autophagic process widely studied in yeast can also be fully reconstituted in human tissues and open the possibility to explore the relevance of the autophagin-based proteolytic system in the induction; regulation, and execution of autophagy.
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页码:3671 / 3678
页数:8
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