title: Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity.
abstract: Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1107, USA.
authors.forename: Annerleim
authors.initials: A
authors.lastname: Walton-Diaz
authors.forename: Sahar
authors.initials: S
authors.lastname: Khan
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bourboulia
authors.forename: Jane B
authors.initials: JB
authors.lastname: Trepel
authors.forename: Len
authors.initials: L
authors.lastname: Neckers
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mollapour
mesh_terms: D000107:Acetylation; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D018833:Chaperonins / Q000378:metabolism; D021983:Cyclophilins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D010766:Phosphorylation; D000071876:Prostaglandin-E Synthases; D011499:Protein Processing, Post-Translational; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D018797:Cell Cycle Proteins; D018833:Chaperonins; D021983:Cyclophilins; D018841:HSP90 Heat-Shock Proteins; D018398:Homeodomain Proteins; D019746:Intramolecular Oxidoreductases; D018832:Molecular Chaperones; D000071876:Prostaglandin-E Synthases; D025521:Tumor Suppressor Proteins; C515652:AHSA1 protein, human; C498362:CDC37 protein, human; C476884:HOPX protein, human; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D