Ask about this productRelated genes to: ZDHHC17 Blocking Peptide
- Gene:
- ZDHHC17 NIH gene
- Name:
- zinc finger DHHC-type containing 17
- Previous symbol:
- -
- Synonyms:
- HIP14, HYPH, KIAA0946
- Chromosome:
- 12q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-14
- Date modifiied:
- 2016-11-09
Related products to: ZDHHC17 Blocking Peptide
Related articles to: ZDHHC17 Blocking Peptide
- Uncontrolled cell cycle progression is a hallmark of cancer, tightly regulated by both intrinsic and extrinsic stimuli. However, the role of fatty acids, in particular palmitic acid, in cell cycle control remains incompletely understood. Here, we observe that inhibition of protein palmitoylation by administrating 2-bromohexadecanoic acid (2-BP) or depleting ZDHHC17, leads to profound cell cycle arrest. Mechanistically, ZDHHC17 palmitoylates CDK4, thereby facilitating its interaction with cyclin D1 (encoded by CCND1), a process depending on TRAF6-mediated K11-linked ubiquitination of CDK4. While, blockade of either palmitoylation or ubiquitination markedly reduces CDK4 kinase activity, resulting in cell cycle arrest and suppressed tumor growth. Furthermore, Zdhhc17-depletion displays reduced cell cycle progression and immune response in a high fat diet (HFD)-feeding mouse model. Clinically, high ZDHHC17 expression is positively correlated with non-response to anti-PD-1 therapies in cancer patients, partially due to CDK4-mediated repression of PD-L1. Thereby, we propose a rational combination strategy of employing CDK4 inhibitors with immune checkpoint blockers (ICBs) to overcome ZDHHC17-driven cancers. In sum, our study uncovers a novel cell cycle control mechanism by ZDHHC17-mediated palmitoylation and TRAF6-mediated ubiquitination of CDK4, presenting a potential therapeutic avenue by targeting the ZDHHC17-TRAF6-CDK4 axis for cell cycle dysregulated cancers. - Source: PubMed
Publication date: 2026/05/14
Wang ZekangSong PeipeiWu XuejiWang LeiXie WeiFeng PinningCheng ChaoGuo Jianping - Emerging evidence suggests that protein palmitoylation plays a critical role in regulating cellular signaling, yet its involvement in skin aging remains largely unexplored. Additionally, the epigenetic regulation of palmitoylation-related genes in age-related dermal changes has not been systematically studied. This research aimed to investigate the causal relationship between palmitoylation genes, DNA methylation, and facial skin aging using Mendelian randomization (MR) methods. - Source: PubMed
Publication date: 2025/12/18
Cai XueyaoLi WeidongShi WenjunDing XiaCai Yuchen - This work examined the causal link between palmitoylation-related genes and Parkinson's disease (PD) by Mendelian randomization (MR). We conducted two-sample Mendelian randomization utilizing genome-wide association study (GWAS) summary statistics. Expression quantitative trait loci (eQTL) data for palmitoylation genes were sourced from eQTLGen, whilst PD data were derived from the GWAS Catalogue (15,056 cases, 12,637 controls) and FinnGen (4,681 cases, 407,500 controls). Instrumental variables (p < 5 × 10⁻⁶, r < 0.1) were examined using inverse-variance weighted (IVW) regression, along with weighted median, MR-Egger, and Summary-data-based MR (SMR) methods. Sensitivity analyses evaluated pleiotropy and resilience. The IVW analysis revealed significant correlations with Parkinson's disease for ZDHHC14 (OR = 1.09, P = 0.037), ZDHHC17 (OR = 1.18, P = 0.002), ZDHHC2 (OR = 1.16, P = 0.039), ZDHHC20 (OR = 0.82, P = 0.019), and ZDHHC8 (OR = 1.24, P = 0.022). SMR validation corroborated solely ZDHHC8 (OR = 1.35, P = 0.040). Replication in FinnGen corroborated ZDHHC1, ZDHHC13, ZDHHC17, and ZDHHC8. No heterogeneity or pleiotropy was observed (P > 0.05). ZDHHC8 has a strong causative relationship with PD, suggesting that palmitoylation dysregulation plays a role in disease etiology. These findings underscore synaptic dysfunction as a viable therapeutic target. - Source: PubMed
Publication date: 2025/10/21
Qiu JinYang JialiZhu RuisenXian DeHaiYang Kaiwen - Regulated exocytosis controls key cellular functions ranging from neurotransmitter release to the secretion of immune mediators, and its disruption is associated with numerous pathologies. The cytotoxic activity of lymphocytes is particularly dependent on regulated and polarized lytic granule delivery toward infected or malignant cells. Although genetic and mechanistic studies have identified factors regulating exocytosis in cytotoxic lymphocytes, a systematic mapping of the relevant factors and their relationships is lacking. Through a genome-scale CRISPR knockout screen in a human natural killer cell line, we characterized a complex genetic network regulating cytotoxic granule exocytosis, with lipid metabolism and protein lipidation among the most prominent pathways. By combining global protein palmitoylation and lipidomic studies, we found that ZDHHC17 drives palmitoylation of the core SNARE complex protein SNAP23 to target cytotoxic granules to GM1-rich lipid rafts whose assembly is controlled by serine palmitoyltransferase. In summary, our study identifies previously unrecognized factors essential for cytotoxic function in human lymphocytes and uncovers how lipid metabolism and protein palmitoylation are involved in the process of regulated exocytosis. - Source: PubMed
Publication date: 2025/10/17
Kalinichenko ArtemHuemer JakobHumer TheresaHaimel MatthiasSvaton MichaelSocquet-Juglard NicolasCasoni Giovanna PerinettiPrakash Celinevon der Linde MaximilianPazmandi Juliavan de Wetering CherylNunez-Fontarnau JavierKamnev AntonGiuliani SarahJaeger Martin GHahn ElisaDobner SarahRukavina AndreaSylvander EliseSeigner JacquelineRashkova ChristinaHoeger BirgitTraxlmayr Michael WLehner ManfredBryceson Yenan TSaarela JannaHannich ThomasCastanon IrinkaWinter GeorgDupré LoïcBoztug Kaan - Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs. - Source: PubMed
Publication date: 2025/07/09
Yang XuewenZhang YanweiLeng XiaopingWang YanyingGong ManyuLiu DongpingLi HaodongDu ZhiyuanWang ZhuoXuan LinaZhang TingSun HanZhang XiyangLiu JieLiu TongGong TiantianLi ZhengyangLiang ShengqiSun LihuaJiao LeiYang BaofengZhang Ying