Kraemer, Oliver H. and Mahboobi, Siavosh and Sellmer, Andreas (2014) Drugging the HDAC6-HSP90 interplay in malignant cells. TRENDS IN PHARMACOLOGICAL SCIENCES, 35 (10). pp. 501-509. ISSN 0165-6147, 1873-3735
Full text not available from this repository. (Request a copy)Abstract
Acetylation and deacetylation cycles regulate crucial biological processes. The enzymes deacetylating lysine residues are termed histone deacetylases (HDACs). Eighteen deacetylases have been isolated from mammalian cells. There is an intense search underway for individual functions of these enzymes and for selective histone deacetylase inhibitors (HDACi). HDAC6 in particular has unique cytoprotective functions that rely on its ability to ensure protein homeostasis and to prevent protein aggregation. The chaperone heat shock protein 90 (HSP90) also safeguards proteins and is deacetylated by HDAC6. Current data illustrate the complexity and importance of the HDAC6-HSP90 interplay. In this review, we discuss how recently identified HSP90-dependent regulators of post-translational modifications (PTMs) of HDAC6 dictate its functions, and how HDACi-induced acetylation of HSP90 might control oncologically relevant proteins, especially in leukemic cells. Additionally, we discuss small molecules blocking HDAC6 and how such agents could become therapeutically relevant. We summarize structure-function relationships that determine the specificity of drugs against HDAC6.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HISTONE DEACETYLASE 6; ACUTE MYELOID-LEUKEMIA; HSP90 CHAPERONE FUNCTION; THERAPEUTIC TARGETS; HDAC6 INHIBITOR; ACETYLATION; BINDING; EXPRESSION; PHOSPHORYLATION; DEGRADATION; Acetylation; cancer; HDAC6; HDAC6 inhibitor; HSP90; leukemia |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Petra Gürster |
| Date Deposited: | 06 Aug 2020 14:26 |
| Last Modified: | 06 Aug 2020 14:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9457 |
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