Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens

Jörn Dengjel, Maria Høyer-Hansen, Maria Nielsen, Tobias Eisenberg, Lea M Harder, Søren Schandorff, Thomas Farkas, Thomas Kirkegaard, Andrea C Becker, Sabrina Schroeder, Katja Vanselow, Emma Lundberg, Mogens M Nielsen, Anders R Kristensen, Vyacheslav Akimov, Jakob Bunkenborg, Frank Madeo, Marja Jäättelä, Jens S. Andersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftMolecular and Cellular Proteomics
Vol/bind11
Udgave nummer3
Sider (fra-til)M111.014035
ISSN1535-9476
DOI
StatusUdgivet - 2012

Fingeraftryk

Proteins
Gene encoding
Proteasome Endopeptidase Complex
Sirolimus
Yeast
Proteomics
Autophagosomes
Chemical activation
Cells
Amino Acids
Degradation
Chemical analysis
concanamycin A
Datasets

Citer dette

Dengjel, Jörn ; Høyer-Hansen, Maria ; Nielsen, Maria ; Eisenberg, Tobias ; Harder, Lea M ; Schandorff, Søren ; Farkas, Thomas ; Kirkegaard, Thomas ; Becker, Andrea C ; Schroeder, Sabrina ; Vanselow, Katja ; Lundberg, Emma ; Nielsen, Mogens M ; Kristensen, Anders R ; Akimov, Vyacheslav ; Bunkenborg, Jakob ; Madeo, Frank ; Jäättelä, Marja ; Andersen, Jens S. / Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. I: Molecular and Cellular Proteomics. 2012 ; Bind 11, Nr. 3. s. M111.014035.
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abstract = "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.",
author = "J{\"o}rn Dengjel and Maria H{\o}yer-Hansen and Maria Nielsen and Tobias Eisenberg and Harder, {Lea M} and S{\o}ren Schandorff and Thomas Farkas and Thomas Kirkegaard and Becker, {Andrea C} and Sabrina Schroeder and Katja Vanselow and Emma Lundberg and Nielsen, {Mogens M} and Kristensen, {Anders R} and Vyacheslav Akimov and Jakob Bunkenborg and Frank Madeo and Marja J{\"a}{\"a}ttel{\"a} and Andersen, {Jens S.}",
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doi = "10.1074/mcp.M111.014035",
language = "English",
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pages = "M111.014035",
journal = "Molecular and Cellular Proteomics",
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Dengjel, J, Høyer-Hansen, M, Nielsen, M, Eisenberg, T, Harder, LM, Schandorff, S, Farkas, T, Kirkegaard, T, Becker, AC, Schroeder, S, Vanselow, K, Lundberg, E, Nielsen, MM, Kristensen, AR, Akimov, V, Bunkenborg, J, Madeo, F, Jäättelä, M & Andersen, JS 2012, 'Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens', Molecular and Cellular Proteomics, bind 11, nr. 3, s. M111.014035. https://doi.org/10.1074/mcp.M111.014035

Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. / Dengjel, Jörn; Høyer-Hansen, Maria; Nielsen, Maria; Eisenberg, Tobias; Harder, Lea M; Schandorff, Søren; Farkas, Thomas; Kirkegaard, Thomas; Becker, Andrea C; Schroeder, Sabrina; Vanselow, Katja; Lundberg, Emma; Nielsen, Mogens M; Kristensen, Anders R; Akimov, Vyacheslav; Bunkenborg, Jakob; Madeo, Frank; Jäättelä, Marja; Andersen, Jens S.

I: Molecular and Cellular Proteomics, Bind 11, Nr. 3, 2012, s. M111.014035.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens

AU - Dengjel, Jörn

AU - Høyer-Hansen, Maria

AU - Nielsen, Maria

AU - Eisenberg, Tobias

AU - Harder, Lea M

AU - Schandorff, Søren

AU - Farkas, Thomas

AU - Kirkegaard, Thomas

AU - Becker, Andrea C

AU - Schroeder, Sabrina

AU - Vanselow, Katja

AU - Lundberg, Emma

AU - Nielsen, Mogens M

AU - Kristensen, Anders R

AU - Akimov, Vyacheslav

AU - Bunkenborg, Jakob

AU - Madeo, Frank

AU - Jäättelä, Marja

AU - Andersen, Jens S.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1074/mcp.M111.014035

DO - 10.1074/mcp.M111.014035

M3 - Journal article

C2 - 22311637

VL - 11

SP - M111.014035

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 3

ER -