6533b7d8fe1ef96bd1269b9c

RESEARCH PRODUCT

Identification of HSP90 as a new GABARAPL1 (GEC1)-interacting protein

Annick FraichardMichaël Boyer-guittautWilfrid BoireauFatima Zahra ChakramaMichèle JouvenotGilles DespouyRégis Delage-mourrouxSophie CroizierStéphanie Seguin-pyPatrick DucoroyGé Raldine LucchiJaclyn Nicole Le Grand

subject

LeupeptinsLactams MacrocyclicGABARAPATG8Blotting WesternLactacystinCysteine Proteinase InhibitorsBiologyBiochemistryMass SpectrometryCell Linechemistry.chemical_compoundCell Line TumorMG132BenzoquinonesAnimalsHumansImmunoprecipitationHSP90 Heat-Shock ProteinsReceptorAdaptor Proteins Signal TransducingMicroscopy ConfocalHEK 293 cellsGeneral MedicineHsp90RatsBiochemistrychemistryProteasomebiology.proteinMicrotubule-Associated Proteins

description

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.

yearjournalcountryeditionlanguage
2011-05-25Biochimie
https://doi.org/10.1016/j.biochi.2011.11.006