title: The dynamic interactome of human Aha1 upon Y223 phosphorylation.
abstract: Heat Shock Protein 90 (Hsp90) is an essential chaperone that supports the function of a wide range of signaling molecules. Hsp90 binds to a suite of co-chaperone proteins that regulate Hsp90 function through alteration of intrinsic ATPase activity. Several studies have determined Aha1 to be an important co-chaperone whose binding to Hsp90 is modulated by phosphorylation, acetylation and SUMOylation of Hsp90 [1], [2]. In this study, we applied quantitative affinity-purification mass spectrometry (AP-MS) proteomics to understand how phosphorylation of hAha1 at Y223 altered global client/co-chaperone interaction [3]. Specifically, we characterized and compared the interactomes of Aha1-Y223F (phospho-mutant form) and Aha1-Y223E (phospho-mimic form). We identified 99 statistically significant interactors of hAha1, a high proportion of which (84%) demonstrated preferential binding to the phospho-mimic form of hAha1. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository [4] with the dataset identifier PXD001737.
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Wolfgeher
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Dunn
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Woodford
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bourboulia
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.affiliation: Department of Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA ; Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mollapour
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kron
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA ; Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Truman
keywords: Aha1; Cancer; Chaperones; Co-chaperones; Hsp90; Interactome; Phosphorylation; Proteomics