ABHD6
- Known as:
- ABHD6
- Catalog number:
- Y214060
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ABHD6
Related genes to: ABHD6
- Gene:
- ABHD6 NIH gene
- Name:
- abhydrolase domain containing 6
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 3p14.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-13
- Date modifiied:
- 2018-08-22
Related products to: ABHD6
Related articles to: ABHD6
- Hepatocellular carcinoma (HCC) frequently develops resistance to lenvatinib, a frontline tyrosine kinase inhibitor. Resistance arises from heterogeneous mechanisms involving metabolic reprogramming and mitochondrial adaptation, implicating regulators of these processes as potential therapeutic targets. Here, we identified α/β hydrolase domain containing 6 (ABHD6) as a critical driver of lenvatinib resistance by perturbing mitochondrial dynamics. Ligand-binding at the S148 catalytic site allosterically controlled a molecular switch between canonical enzymatic and non-canonical scaffolding functions of ABHD6, and the pro-resistance function was independent of catalysis but required an unoccupied catalytic site. In resistant HCC, the Warburg effect elevated lactate, leading to K245 lactylation of ABHD6. This modification triggered the mitochondrial translocation of ABHD6, where it functioned as a scaffold that competitively bound the fission regulator FIS1 and displaced DRP1. Disruption of the fission machinery stabilized hyperfused mitochondria, thereby conferring lenvatinib resistance by suppressing drug-induced apoptosis and ROS generation. Both inhibiting lactate production and enforcing occupancy of the S148 site with substrates or a specific inhibitor blocked formation of the ABHD6-FIS1 complex, reactivated mitochondrial fission, and restored lenvatinib sensitivity. This study identified a lactate-driven functional switch in ABHD6 and established that targeting this allosteric mechanism is an effective therapeutic strategy to overcome lenvatinib resistance. - Source: PubMed
Publication date: 2026/03/20
Sun YueningLuo ChengjuYang HuiYe JiaxinSong FengliangYi QuanhuaZou WenhaoHuang YanFan XiangjunWang LeiZhang YananDing QianZhu YizhunTang Zhiyuan - The enzymatic function of ABHD6 on insulin secretion and insulin resistance is well documented. However, its non-enzymatic function, especially its effects on selective hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) is completely unexplored. ABHD6 is elevated under conditions of diet-induced obesity and aging. To define the role of ABHD6 in liver physiology, we generated liver-specific ABHD6 knockout mice, as well as liver specific overexpression of native and enzymatic inactive mutant ABHD6 mouse models. We demonstrated that ABHD6 is an unidentified regulator of selective hepatic insulin resistance and contributes to MASLD and liver fibrosis. Furthermore, we found that non-enzymatic ABHD6, rather than its enzymatic form, contributes to this regulation. Mechanistically, we found that ABHD6 translocated into the nucleus and interacted with Akt/FoxO1 axis to regulate its function. In addition, knockdown of FoxO1 in primary hepatocytes or overexpression of constitutively active mutant FoxO1 by AAV approach could completely abolish the effects of ABHD6 on glucose tolerance and gluconeogenesis. Our study reveals an entirely different mechanism underlying selective hepatic insulin resistance that involves a previously unknown non-enzymatic function of ABHD6. This study opens an avenue for the development of a novel class of ABHD6 inhibitors to treat MASLD and liver fibrosis. - Source: PubMed
Publication date: 2026/02/13
Li GuannanMaeyens Laurence TYin JiyuanFuncke Jan-BerndJoung ChanminLi RuizhenXu ZiyingWu TingLi XinJiang NisiEkane MbolleLopez Maria PaulaCao PengjuHe SijiaSalmon Adam BMadiraju S R MurthyPrentki MarcBai JuliNelson James FHan XianlinZhu YiZhao Shangang - Cisplatin-induced ototoxicity is a detrimental side effect of chemotherapy leading to hearing loss, for which no treatments are currently available. Despite the growing recognition of the endocannabinoid (eCB) system (ECS) as a significant contributor to different physiological and pathological processes, its role in hearing remains poorly investigated. To fill this knowledge gap, we performed a molecular profiling of the ECS in auditory hair cell (HC)-like UB/OC1 cells derived from the mouse organ of Corti (OC), demonstrating the presence of the main eCBs-binding receptors and metabolic enzymes along with the major eCBs (N-arachidonoylethanolamine, AEA, and 2-arachidonoylglycerol, 2-AG) and additional eCB-like compounds. Subsequently, we established an in vitro model of cisplatin-induced ototoxicity, which was characterized by the downregulation of the HC marker myosin 7a (Myo 7a), and activation of nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) associated with caspase-3-mediated cell death. In this model, we observed a downregulation of cannabinoid receptor 2 (CBR), diacylglycerol lipase β (DAGLβ), and α/β hydrolase domain-containing protein 6 (ABHD6), indicating a perturbation of the 2-AG metabolic pathway. Furthermore, we validated the observed in vitro alterations in the OC of an in vivo model of cisplatin-induced ototoxicity, thereby strengthening the physiological relevance of our findings. Finally, we demonstrated that pharmacological blockade of CBR through SR144528 mitigates cisplatin-induced HC damage via inhibition of caspase-3 cleavage in UB/OC1 HC-like cells, thereby providing novel mechanistic insights into the role of CBR in ototoxicity. Overall, our study demonstrates the involvement of selective elements of the ECS in cisplatin-induced ototoxicity, hence identifying novel potential biomolecular targets for chemotherapy-related side effects. - Source: PubMed
Palaniappan SakthimalaTisi AnnamariaDi Meo CamillaUrbano CristinaFenton Georgina EDella Valle FrancescoFanti FedericoCompagnone DarioNazarè MarcVersnel HuibAramini AndreaAllegretti MarcelloMaccarrone Mauro - Covalent fluorescent probes have emerged as versatile chemical tools to visualise active enzymes in complex biological systems. When tailored for specific applications, ranging from activity-based protein profiling for drug development to high spatiotemporal resolution imaging of enzymatic activities, these probes provide unique insights into rapid lipid metabolism. The recent development of reverse-designing optimised inhibitors into probes, together with improved analytical techniques, is rapidly advancing our ability to resolve enzyme function in great detail. In this mini-review, we summarise the current landscape of covalent fluorescent probes for the 2-arachidonoylglycerol (2-AG) metabolising enzymes (diacylglycerol lipase, monoacylglycerol lipase, ABHD6 and ABHD12), highlighting the discoveries they have enabled and discussing strategies to address gaps where probes remain lacking. - Source: PubMed
Publication date: 2026/01/18
Puijmbroeck Nick D Fvan der Stelt Mario - A key endocannabinoid, 2-arachidonoyl glycerol (2-AG), regulates sperm hyperactivation in humans via alpha/beta hydrolase domain-containing protein 2 (ABHD2)-mediated CatSper calcium channel activation. However, the role of ABHD2 in mice is unclear, whereas monoacylglycerol lipase (MAGL), ABHD-containing protein 6 (ABHD6), and ABHD-containing protein 12 (ABHD12) modulate 2-AG in the mouse central nervous system (CNS). - Source: PubMed
Zhang XinWu WenjingLi YahuiYang Minghua