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Last update 08 May 2025

ABHD17A

Last update 08 May 2025

Basic Info

Synonyms

ABHD17A, abhydrolase domain containing 17A, depalmitoylase, Abhydrolase domain-containing protein 17A

+ [4]

Introduction

Hydrolyzes fatty acids from S-acylated cysteine residues in proteins (PubMed:26701913). Has depalmitoylating activity towards NRAS (PubMed:26701913). Has depalmitoylating activity towards DLG4/PSD95 (PubMed:26701913). May have depalmitoylating activity towards MAP6 (By similarity).

Drugs associated with ABHD17A

ABD957

Target

ABHD17A

Mechanism

ABHD17A inhibitors

Active Org.

The Scripps Research Institute

Originator Org.

The Scripps Research Institute

Active Indication

Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ABHD17A

100 Translational Medicine associated with ABHD17A

0 Patents (Medical) associated with ABHD17A

Literatures (Medical) associated with ABHD17A

01 Dec 2024·eBioMedicine

Multi-omic characteristics of longitudinal immune profiling after breakthrough infections caused by Omicron BA.5 sublineages

Article

Author: Bao, Yanmin ; Zhang, Yanan ; Gao, George Fu ; Zhao, Xin ; Li, Ying ; Hou, Yali ; Zhang, Rong ; Xiao, Yunfeng ; Ma, Yueyun ; Qiao, Shitong ; Qin, Shijie ; Li, Yanhua ; Dong, Lei

BACKGROUNDOmicron sub-variants breakthrough infections (BTIs) have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. The acute-phase immune status is critical for prognosis, however, the dynamic immune profiling of COVID-19 during the first month after BTIs remains unclear.METHODSIn this study, we monitored the immune dynamics at various timepoints in a longitudinal cohort during the first month post-BTIs through clinical evaluation, single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR)/B cell receptor (BCR) sequencing, and antibody mass spectrometry.FINDINGSSerological analysis revealed limited impairment to functions of major organs, active cellular and humoral immunity at 2 weeks post-BTI, with significant increases in cytokines (CKs) and neutralizing antibody levels. However, 1 month post-BTI, organ function parameters and CK levels reverted to pre-infection levels, whereas neutralizing antibody levels remained high. Notably, scRNA-seq showed that lymphocytes maintained strong antiviral activity and cell depletion at 2 weeks and 1 month post-BTI, with genes CD81, ABHD17A, CXCR4, DUSP1, etc. upregulated, and genes PFDN5, DYNLRB1, CD52, etc. downregulated, indicating that lymphocytes status take longer to recover to normal levels than that routine blood tests revealed. Additionally, T cell-exhaustion associated genes, including LAG3, TIGIT, PDCD1, CTLA4, HAVCR2, and TOX, were upregulated after BTI. TCRs and BCRs exhibited higher clonotypes, mainly in CD8Tem or plasmablast cells, at 2 weeks post-BTI comparing 1 month. More IgG and IgA-type BCRs were found in the groups of 1 month post-BTI, with higher somatic hypermutation, indicating greater maturity. Verification of monoclonal antibodies corresponding to amplified BCRs highlighted the antigen-specific and broad-spectrum characteristics.INTERPRETATIONOur study elucidated the dynamic immune profiling of individuals after Omicron BA.5 sublineages BTI. Strong immune activation, antiviral response, antibody maturation and class transition at 2 weeks and 1 month after BTI may provide essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron sublineage BTI.FUNDINGThis study was supported by the National Key R&D Program of China, the China Postdoctoral Science Foundation, Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, and the Air Force Special Medical Center Science and Technology Booster Program.

01 Nov 2024·Cell Reports

ZDHHC3-mediated SCAP S-acylation promotes cholesterol biosynthesis and tumor immune escape in hepatocellular carcinoma

Article

Author: Wang, Genxin ; Wang, Fubing ; Wu, Mingzhi ; Zeng, Yiqun ; Prochownik, Edward V ; Prochownik, Edward V. ; Li, Jun ; Zhou, Xinyi ; Li, Youjun ; Zhou, Xiaojun

Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4⁺ T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl₄-induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.

01 Dec 2023·Molecular Cell

ZDHHC5-mediated NLRP3 palmitoylation promotes NLRP3-NEK7 interaction and inflammasome activation

Article

Author: Wang, Shuxian ; Ma, Junfeng ; Chen, Liang ; Song, Qibin ; Pei, Huadong ; Zheng, Sihao ; Que, Xiangyong ; Xing, Xiaoke ; An, Ping ; Yao, Yi ; Hou, Chunyan ; Peng, Yihan ; Li, Juanjuan ; Zhang, Pingfeng ; Zhou, Qi

The nucleotide-binding domain (NBD), leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a critical mediator of the innate immune response. How NLRP3 responds to stimuli and initiates the assembly of the NLRP3 inflammasome is not fully understood. Here, we found that a cellular metabolite, palmitate, facilitates NLRP3 activation by enhancing its S-palmitoylation, in synergy with lipopolysaccharide stimulation. NLRP3 is post-translationally palmitoylated by zinc-finger and aspartate-histidine-histidine-cysteine 5 (ZDHHC5) at the LRR domain, which promotes NLRP3 inflammasome assembly and activation. Silencing ZDHHC5 blocks NLRP3 oligomerization, NLRP3-NEK7 interaction, and formation of large intracellular ASC aggregates, leading to abrogation of caspase-1 activation, IL-1β/18 release, and GSDMD cleavage, both in human cells and in mice. ABHD17A depalmitoylates NLRP3, and one human-heritable disease-associated mutation in NLRP3 was found to be associated with defective ABHD17A binding and hyper-palmitoylation. Furthermore, Zdhhc5^-/- mice showed defective NLRP3 inflammasome activation in vivo. Taken together, our data reveal an endogenous mechanism of inflammasome assembly and activation and suggest NLRP3 palmitoylation as a potential target for the treatment of NLRP3 inflammasome-driven diseases.

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ABHD17A

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