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Acetylome Profiling Reveals the Endogenous Substrates of HDAC6

ABSTRACT: HDAC6 inhibitors are novel targeted therapies showing good clinical response in a variety of different malignancies. However, their use and farther development is hampered by the limited knowledge regarding what are the endogenous substrates of HDAC6 enzyme. Here we plan to complete acetylome profiling of HAP1 cells with and without HDAC6 knockout to identify which are the HDAC6 substrates and what are the differences between the wildtype and HDAC6-KO cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yuxin Li

LAB HEAD: Junmin Peng

PROVIDER: PXD026010 | Pride | 2022-11-09

REPOSITORIES: Pride

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Network-based assessment of HDAC6 activity predicts preclinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer.

Zeleke Tizita Z TZ Pan Qingfei Q Chiuzan Codruta C Onishi Maika M Li Yuxin Y Tan Haiyan H Alvarez Mariano J MJ Honan Erin E Yang Min M Chia Pei Ling PL Mukhopadhyay Partha P Kelly Sean S Wu Ruby R Fenn Kathleen K Trivedi Meghna S MS Accordino Melissa M Crew Katherine D KD Hershman Dawn L DL Maurer Matthew M Jones Simon S High Anthony A Peng Junmin J Califano Andrea A Kalinsky Kevin K Yu Jiyang J Silva Jose J

Nature cancer 20221230 2

Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy. Thus, we designed a phase 1b dose-escalation clinical trial to eva ...[more]

PMID: 36585452

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