Post-translational modifications of three members of the human MAP1LC3 family and detection of a novel type of modification for MAP1LC3B

被引:239
作者
He, H
Dang, YJ
Dai, FY
Guo, ZK
Wu, JX
She, XY
Pei, Y
Chen, YJ
Ling, WH
Wu, CQ
Zhao, SY
Liu, JO
Yu, L
机构
[1] Fudan Univ, Inst Genet, State Key Lab Genet Engn, Sch Life Sci, Shanghai 200433, Peoples R China
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Sci & Neurosci, Baltimore, MD 21205 USA
关键词
D O I
10.1074/jbc.M303800200
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
The molecular machinery required for autophagy is highly conserved in all eukaryotes as seen by the high degree of conservation of proteins involved in the formation of the autophagosome membranes. Recently, both yeast Apg8p and its rat homologue Map1lc3 were identified as essential constituents of autophagosome membrane as a processed form. In addition, both the yeast and human proteins exist in two modified forms produced by a series of post-translational modifications including a critical C-terminal cleavage after a conserved Gly residue, and the smaller processed form is associated with the autophagosome membranes. Herein, we report the identification and characterization of three human orthologs of the rat Map1LC3, named MAP1LC3A, MAP1LC3B, and MAP1LC3C. We show that the three isoforms of human MAP1LC3 exhibit distinct expression patterns in different human tissues. Importantly, we found that the three isoforms of MAP1LC3 differ in their post-translation modifications. Although MAP1LC3A and MAP1LC3C are produced by the proteolytic cleavage after the conserved C-terminal Gly residue, like their rat counterpart, MAP1LC3B does not undergo C-terminal cleavage and exists in a single modified form. The essential site for the distinct posttranslation modification of MAP1LC3B is Lys-122 rather than the conserved Gly- 120. Subcellular localization by cell fractionation and immunofluorescence revealed that three human isoforms are associated with membranes involved in the autophagic pathway. These results revealed different regulation of the three human isoforms of MAP1LC3 and implicate that the three isoforms may have different physiological functions.
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页码:29278 / 29287
页数:10
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