Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Aberrant acetylation has been strongly linked to tumorigenesis, and the modulation of acetylation through targeting histone deacetylases (HDACs) is gathering increasing pace as a viable therapeutic strategy. A genome-wide loss-of-function screen identified HR23B, which shuttles ubiquitinated cargo proteins to the proteasome, as a sensitivity determinant for HDAC inhibitor-induced apoptosis. HR23B also governs tumor cell sensitivity to drugs that act directly on the proteasome. The level of HR23B influences the response of tumor cells to HDAC inhibitors, and HR23B is found at high levels in cutaneous T cell lymphoma in situ, a malignancy that responds favorably to HDAC inhibitor-based therapy. These results suggest that deregulated proteasome activity contributes to the anticancer activity of HDAC inhibitors.

Original publication

DOI

10.1016/j.ccr.2008.12.001

Type

Journal article

Journal

Cancer Cell

Publication Date

06/01/2009

Volume

15

Pages

57 - 66

Keywords

Animals, Apoptosis, Biopsy, Cell Line, Tumor, DNA-Binding Proteins, Drug Evaluation, Preclinical, Enzyme Inhibitors, Gene Expression Regulation, Neoplastic, Genome, Histone Deacetylase Inhibitors, Histone Deacetylases, Lymphoma, T-Cell, Cutaneous, Mice, Mice, Knockout, Proteasome Endopeptidase Complex, RNA Interference, Skin Neoplasms, Substrate Specificity