Ask about this productRelated genes to: ACAA1 Blocking Peptide
- Gene:
- ACAA1 NIH gene
- Name:
- acetyl-CoA acyltransferase 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-30
- Date modifiied:
- 2019-03-22
Related products to: ACAA1 Blocking Peptide
Related articles to: ACAA1 Blocking Peptide
- Molecular glues promote protein-protein interactions by enhancing the surface complementarity between proteins. Those that recruit an E3 ubiquitin ligase to a target can elicit ubiquitination and subsequent destruction of the target protein-a mechanism that underpins the field of targeted protein degradation (TPD). Here we explored whether small-molecule binders to the CTLH E3 ligase subunit GID4 could act as molecular glues. We discovered that CLEO4-88 functions as a molecular glue (EC = 12.5 nM) to promote the interaction of GID4 with the peroxisomal thiolase ACAA1 in vitro and in cellulo. An atomic structure of the ternary complex revealed an allosteric mechanism whereby CLEO4-88 binds solely to GID4 and induces a conformational change conducive to binding ACAA1. Biochemical analysis demonstrated that, while ACAA1 cannot be recruited by GID4 to a CTLH holoenzyme for ubiquitination, ternary complex formation inhibits ACAA1 thiolase activity, thus demonstrating potential utility beyond TPD. - Source: PubMed
Publication date: 2026/04/09
Chana Chetan KBen Makhlouf InesKim JaeyounYu April J YMoatti NathalieOrlicky StephenWong Cassandra JBaronijan LeonTang XiaoJingMao DanielLarsen BrettMcGary LauraSeale BrendonMader PavelCeccarelli Derek FBarbulescu PhilipMartin AlbertoDurocher DanielPelletier LaurenceGingras Anne-ClaudeSicheri Frank - Aging is a fundamental biological process that influences cancer development in a context-dependent manner; however, how aging-related programs manifest in hepatocellular carcinoma (HCC) remains incompletely understood. Here, we systematically characterized aging-associated features in HCC by establishing a liver cancer-specific aging signature, termed HCCaging, across more than 2,000 tumor samples from 16 independent cohorts. We comprehensively evaluated its heterogeneity and associations with clinical outcomes, tumor stage, immune infiltration, and therapeutic response. The HCCaging score increased with chronological age, was higher in normal liver than tumor tissues, and elevated in early- versus late-stage tumors. In contrast, 13 previously reported aging- or senescence-related gene sets failed to show consistent patterns across these conditions in HCC. Machine learning models, including gradient boosting machines and random forests, achieved higher accuracy in distinguishing tumor from non-tumor samples using the HCCaging score compared with other 13 aging- or senescence-gene sets across eight independent HCC cohorts. Single-cell transcriptomic profiling revealed that HCCaging increased with age, particularly within epithelial compartments, reaching its highest levels in hepatocytes. Notably, although the proportion of T/NK cells declined with aging, their functional programs, including activated effector function, chemokine/chemokine receptor signaling, cytolytic activity, and pro-inflammatory pathways, were enhanced in older individuals. The HCCaging score, together with key genes ACAA1 and ESR1, were negatively correlated with T/NK cell infiltration, anti-inflammatory activity, and anti-apoptotic signatures, but positively correlated with pro-apoptotic, pro-inflammatory, chemokine, and cytolytic pathways. Furthermore, increased expression of XCL1 and XCL2 in T/NK cells with aging correlated positively with HCCaging, ACAA1, and ESR1, suggesting preserved or even enhanced antitumor potential of T/NK cells in older patients. Collectively, these findings highlight the dual role of aging in liver tumorigenesis. Hepatic aging and enhanced T/NK cell effector function may confer tumor-protective effects, whereas the concomitant decline in overall T/NK cell infiltration likely compromises immunosurveillance, thereby increasing carcinogenic susceptibility in the aging liver. This study provides new insights into the heterogeneity of hepatic aging and its complex interplay with the HCC tumor microenvironment and clinical outcomes. - Source: PubMed
Publication date: 2026/04/06
Yu BinZhang YajuanTang YongHu MeilingWei Jinfen - The aroma quality of oolong tea depends on both processing techniques and cultivars; however, the molecular basis underlying cultivar suitability remains unclear. Six cultivars of tea (Camellia sinensis (L.) O. Kuntze), namely 'Huangdan', 'Meizhan', 'Tieguanyin', 'Jiaming No. 1', 'Yingshuang', and 'Fuding Dabaicha', were analyzed using integrated metabolomic and transcriptomic approaches. Dynamic changes in volatile compounds were monitored during processing, and five key metabolites, including indole, α-farnesene, (E)-nerolidol, (E)-3-hexyl acetate, and jasmine lactone, were identified as markers of processing suitability. Comparative co-expression network analysis between the suitable cultivar 'Huangdan' and the unsuitable cultivar 'Jiaming No. 1' revealed distinct expression patterns of genes involved in aroma biosynthesis, including anthranilate phosphoribosyl ester isomerase (trpF), (3S,6E)-nerolidol synthase (NES1), farnesyl diphosphate farnesyltransferase (FDFT1), diphosphomevalonate decarboxylase (MVD), geranyl diphosphate synthase type II (GGPS), acyl-CoA oxidase (ACX), 1,2-oxidophytodienoate reductase (OPR), acetyl-CoA acyltransferase I (ACAA1), and jasmonic acid-O-methyltransferase (JMT). These findings elucidate the molecular mechanisms underlying cultivar suitability in oolong tea and provide a foundation for cultivar selection and processing optimization. - Source: PubMed
Publication date: 2026/03/18
He ChangLi YuchuanZhou JingtaoZhang DeYu ZhiNi Dejiang - Frailty, a clinical state of increased vulnerability to stressors with aging, imposes significant strain on healthcare systems. Its genetic underpinnings remain incompletely explored, highlighting the need to identify novel therapeutic targets for aging. - Source: PubMed
Publication date: 2026/04/01
Zhong JiaYuYuan MingHaoZhou EnHu Shuo - A metabolomics study was conducted on serum and liver samples from mice with alcoholic liver injury induced by the National Institute on Alcohol Abuse and Alcoholism(NIAAA). This was combined with network pharmacology to investigate the ameliorative effect of Tricholoma matsutake extracts on alcoholic liver injury in mice and its underlying mechanism. Serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and triglyceride(TG) were measured, while liver pathological changes were assessed by hematoxylin-eosin(HE) staining. Moreover, differential metabolites in serum and liver were detected by gas chromatography-mass spectrometry(GC-MS), and potential targets of T. matsutake extracts were analyzed via network pharmacology. The predicted targets were compared with those associated with differential metabolites to explore key targets involved in the amelioration of alcoholic liver injury by the extract. The results showed that, compared with the pathological model group, the T. matsutake extracts treatment group showed significantly reduced serum ALT, AST, and TG levels, along with improved lipid vacuolation and hepatocyte morphology, indicating a significant ameliorative effect of the extract on alcoholic liver injury in mice. The metabolomics results revealed that the extract modulated 12 differential metabolites in liver tissues, including glucose, glutamate, leucine, and phenylalanine, and 31 differential metabolites in serum, including alanine, cholesterol, glucose, lactose, and methionine. Further network pharmacology analysis suggested that T. matsutake extracts may ameliorate alcoholic liver injury primarily by targeting pathways related to Myc and Cat, influencing genes such as Aldh9a1, Aldh3a2, Aldh2, Hsd17b4, Ehhadh, Acox1, Acaa1, Acot1, and Gls. These were mainly involved in five metabolic pathways: cysteine and methionine metabolism, arginine biosynthesis, and alanine, aspartate, and glutamate metabolism. In conclusion, T. matsutake extracts may ameliorate alcoholic liver injury in mice by regulating amino acid metabolism and glucose metabolism through pathways associated with Myc and Cat. - Source: PubMed
Yuan Pei-ZhiTang Cheng-LunZhang QiZhang Tian-YaoChen Jia-XiYang LiuHe Zhi-YanCao Xiao-NianSun Yang