HDAC3 and HDAC8 PROTAC dual degrader reveals roles of histone acetylation in gene regulation
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ABSTRACT:
PROVIDER: PRJNA947763 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23944226_1.fastq.gz | Fastqsanger.gz | |||
| SRR23944226_2.fastq.gz | Fastqsanger.gz | |||
| SRR23944227_1.fastq.gz | Fastqsanger.gz | |||
| SRR23944227_2.fastq.gz | Fastqsanger.gz | |||
| SRR23944228_1.fastq.gz | Fastqsanger.gz |
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Project description:HDAC3 and HDAC8 are members of class I deacetylases involved in several biological mechanisms and represent a highly sought-after therapeutic target for drug development. It is historically challenging to develop selective deacetylase inhibitors due to their conserved catalytic domains. HDAC3 also has deacetylase-independent activity, which cannot be blocked by conventional enzymatic inhibitors. Recent advances in proteolysis-targeting chimeras (PROTACs) provides an opportunity to eliminate the whole protein selectively, abolishing both enzymatic and scaffolding functions. Here, we report a novel HDAC3/8 dual degrader YX968 that induces highly potent, rapid and selective degradation of both HDAC3 and HDAC8 without trigging pan-HDAC inhibitory effects. Unbiased quantitative proteomics experiments further confirmed its high selectivity. This dual-specific degrader specifically ablates cellular pathways attributed to HDAC3 and HDAC8 and exhibits high potency in killing cancer cells. YX968 represents a new probe for dissecting the complex biological functions of HDAC3 and HDAC8.
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