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

作者：Seguin Py Stephanie; Lucchi Geraldine; Croizier Sophie; Chakrama Fatima Z; Despouy Gilles; Le Grand Jaclyn N; Ducoroy Patrick; Boireau Wilfrid; Boyer Guittaut Michael; Jouvenot Michele; Fraichard Annick; Delage Mourroux Regis^*

来源：Biochimie, 2012, 94(3): 748-758.

DOI：10.1016/j.biochi.2011.11.006

• 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG):GABA(A) receptor-protein-like 1 (GABARAPL1)
• Glandular epithelial cell 1 (GEC1)
• Heat shock protein 90 (HSP90)
• Michigan cancer foundation-7 (MCF-7)
• Proteasome inhibitors

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.

• 出版日期2012-3