Identification of Autophagosome-associated Proteins and Regulators by Quantitative Proteomic Analysis and Genetic Screens

被引：115

作者：

Dengjel, Joern ^{[1
,2
,3
,4
]}

Hoyer-Hansen, Maria ^{[5
,6
]}

Nielsen, Maria O. ^{[1
]}

Eisenberg, Tobias ^{[7
]}

Harder, Lea M. ^{[1
]}

Schandorff, Soren ^{[1
]}

Farkas, Thomas ^{[5
,6
]}

Kirkegaard, Thomas ^{[5
,6
]}

Becker, Andrea C. ^{[2
,3
]}

Schroeder, Sabrina ^{[7
]}

Vanselow, Katja ^{[1
]}

Lundberg, Emma ^{[8
]}

Nielsen, Mogens M. ^{[1
]}

Kristensen, Anders R. ^{[1
]}

Akimov, Vyacheslav ^{[1
]}

Bunkenborg, Jakob ^{[1
]}

Madeo, Frank ^{[7
]}

Jaattela, Marja

Andersen, Jens S.

机构：

[1] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark

[2] Univ Freiburg, Freiburg Inst Adv Studies LifeNet, D-79104 Freiburg, Germany

[3] Univ Freiburg, Ctr Biol Syst Anal ZBSA, D-79104 Freiburg, Germany

[4] Univ Freiburg, Ctr Biol Signaling Studies BIOSS, D-79104 Freiburg, Germany

[5] Danish Canc Soc, Apoptosis Dept, DK-2100 Copenhagen, Denmark

[6] Danish Canc Soc, Ctr Genotox Stress Res, DK-2100 Copenhagen, Denmark

[7] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[8] Royal Inst Technol, SE-10691 Stockholm, Sweden

来源：

MOLECULAR & CELLULAR PROTEOMICS | 2012年 / 11卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

MONITORING AUTOPHAGY; SELECTIVE AUTOPHAGY; DEGRADATION; UBIQUITIN; STARVATION; LYSOSOMES; PATHWAYS; DYNAMICS; SILAC;

D O I：

10.1074/mcp.M111.014035

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome- associated proteins were dependent on stimulus, but a core set of proteins was stimulus- independent. Remarkably, proteasomal proteins were abundant among the stimulus- independent common autophagosome- associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome- associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection. Molecular & Cellular Proteomics 11: 10.1074/ mcp.M111.014035, 1-17, 2012.

引用

页数：17

共 59 条

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