title: Identification of HSP90 as a new GABARAPL1 (GEC1)-interacting protein.
abstract: GABARAPL1 belongs to the small family of GABARAP proteins (including GABARAP, GABARAPL1 and GABARAPL2/GATE-16), one of the two subfamilies of the yeast Atg8 orthologue. GABARAPL1 is involved in the intracellular transport of receptors, via an interaction with tubulin and GABA(A) or kappa opioid receptors, and also participates in autophagy and cell proliferation. In the present study, we identify the HSP90 protein as a novel interaction partner for GABARAPL1 using GST pull-down, mass spectrometry and coimmunoprecipitation experiments. GABARAPL1 and HSP90 partially colocalize in MCF-7 breast cancer cells overexpressed Dsred-GABARAPL1 and in rat brain. Moreover, treatment of MCF-7 cells overexpressed FLAG-GABARAPL1-6HIS with the HSP90 inhibitor 17-AAG promotes the GABARAPL1 degradation, a process that is blocked by proteasome inhibitors such as MG132, bortezomib and lactacystin. Accordingly, we demonstrate that HSP90 interacts and protects GABARAPL1 from its degradation by the proteasome.
authors: Université de Franche-Comté, EA3922 Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, IFR133, U.F.R. Sciences et Techniques, 16 route de Gray, 25030 Besançon Cedex, France.
authors: Stéphanie
authors: S
authors: Seguin-Py
authors: Géraldine
authors: G
authors: Lucchi
authors: Sophie
authors: S
authors: Croizier
authors: Fatima Z
authors: FZ
authors: Chakrama
authors: Gilles
authors: G
authors: Despouy
authors: Jaclyn N
authors: JN
authors: Le Grand
authors: Patrick
authors: P
authors: Ducoroy
authors: Wilfrid
authors: W
authors: Boireau
authors: Michaël
authors: M
authors: Boyer-Guittaut
authors: Michèle
authors: M
authors: Jouvenot
authors: Annick
authors: A
authors: Fraichard
authors: Régis
authors: R
authors: Delage-Mourroux
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016227:Benzoquinones; D015853:Cysteine Proteinase Inhibitors; C430503:GABARAPL1 protein, human; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D007976:Leupeptins; D008869:Microtubule-Associated Proteins; C112765:tanespimycin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde