Ask about this productRelated genes to: ZDHHC24 Blocking Peptide
- Gene:
- ZDHHC24 NIH gene
- Name:
- zinc finger DHHC-type containing 24
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 11q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-03-14
- Date modifiied:
- 2016-02-15
Related products to: ZDHHC24 Blocking Peptide
Related articles to: ZDHHC24 Blocking Peptide
- Recent studies have reported that palmitoylation plays a pivotal role in the process of angiogenesis, as well as in the motility and migration of endothelial cells (ECs). However, the role of palmitoylation in the pathogenesis of intracranial aneurysms (IAs) has not yet been systematically investigated. Moreover, alterations in DNA methylation and the expression of IA-related genes have not received sufficient attention. - Source: PubMed
Yuan HaoLi CanFeng XinLin JianchengHuang ChiHuang MengshiDuan Chuanzhi - METTL3, a key RNA N-methyladenosine (mA) methyltransferase, plays essential roles in cell fate regulation and tissue homeostasis, yet therapeutic strategies to enhance its activity remain unexplored. Here, we profile the S-palmitoylation landscape during embryonic stem cell differentiation and observe increased METTL3 S-palmitoylation at cysteine 376 during mesodermal commitment. This modification is catalyzed by ZDHHC24 and reversed by ABHD17A. METTL3 C376S mice exhibit cartilage defects and exacerbated osteoarthritis (OA). Through AI-guided screening, we identify Isoborneol as a small molecule that enhances METTL3 S-palmitoylation by disrupting its interaction with ABHD17A. Isoborneol treatment alleviates joint degeneration and preserves cartilage integrity in OA models. Mechanistically, S-palmitoylation promotes METTL3 condensate formation in proximity to ribosomes, facilitating its cytoplasmic spatial compartmentalization. This condensate state suppresses chaperone-mediated autophagy, thereby enhancing METTL3 protein stability. Our findings reveal S-palmitoylation as a regulatory mechanism governing METTL3 localization and turnover and establish a pharmacological strategy for restoring METTL3 activity in OA. - Source: PubMed
Publication date: 2026/02/19
Qin WeiWei JiatianLi FuxiWang LiqiuZhang QinkaiChen JianLu PengLong TengLiu AijunCao JizhaoDeng YichengZhang HuantianChen DongfengCui JunZhao Wei - Serine-arginine protein kinase 1 (SRPK1) is a major protein kinase involved in mRNA splicing, cell cycle, and endothelial function. Recent studies have highlighted a close relationship between palmitic acid (PA) and endothelial cell ferroptosis. Here, we demonstrate that PA promotes the ubiquitination-dependent degradation of SRPK1 mediated by the E3 ubiquitin ligase mindbomb 1 (MIB1) at lysine 494. Moreover, SRPK1 S-palmitoylation is catalyzed by zinc-finger DHHC S-acyltransferase 24 (ZDHHC24) at cysteines 188/502/647 and deacylated by acyl protein thioesterase 1 (APT1). The dynamic S-palmitoylation of SRPK1 can strengthen SRPK1-MIB1 interaction, facilitate its ubiquitination, and thereby affect protein stability. Furthermore, SRPK1 modulates the phosphorylation of p53 tumor suppressor protein (p53) at serine 15, which may promote its nuclear translocation and activation under PA stimulation or in high-fat-diet-fed animal models. The crucial effect of SRPK1 on p53 activation contributes to the suppression of endothelial cell ferroptosis in the context of lipid accumulation. Additionally, in silico screening reveals that 4'-O-Methylochnaflavone interacts with SRPK1, which effectively stabilizes SRPK1 and alleviates PA-induced ferroptosis. Collectively, these findings underscore the critical role of PA in regulating endothelial cell ferroptosis via SRPK1 S-palmitoylation and p53 activation, providing potential therapeutic strategies for dyslipidemia-related erectile dysfunction. - Source: PubMed
Publication date: 2026/01/29
Tan Xiao-HuiLi Ke-FanYuan Yi-MingXia Man-ChengZhao Fang-ZhouYing Hong-GangZhou ZhuoGao Peng-ChaoXie Guo-QingLi Xue-SongJiang HuiGuan Rui-Li - Colorectal cancer responds poorly to immune checkpoint blockade in most patients with microsatellite-stable (MSS) tumors, highlighting the need for alternative targets. B7H3 (CD276) is an immune checkpoint protein that is frequently overexpressed in tumors, but how it is maintained at high protein levels is unclear. Here we show that palmitic acid (PA) promotes B7H3 palmitoylation by the palmitoyltransferase ZDHHC24 at cysteine 496. This modification prevents B7H3 from binding to sequestosome 1 (SQSTM1, also called p62), limiting autophagic degradation and stabilizing B7H3, which suppresses CD8 T cell antitumor activity. Disrupting this pathway by mutating cysteine 496, or by deleting Zdhhc24 in a colitis-associated colorectal cancer (CAC) mouse model, enhances CD8 T cell responses. We also develop a cell-penetrant peptide that blocks the ZDHHC24-B7H3 interaction, boosts antitumor immunity, and synergizes with blockade of programmed cell death protein 1 (PD-1). These findings identify B7H3 palmitoylation as a targetable metabolic-immune node for colorectal cancer immunotherapy. - Source: PubMed
Publication date: 2026/01/19
Rao ZejunHuang ChangshengWu QiLi MaoLiu AnyiZhu TongYang WangshuoYin LanlanZhu ShengyuShe XiaoweiYu ChengxinLiu LangLi PengchengBai YucongZhang DongjingXie TianciLiu XiangLiu LuXu FengWang GuihuaHu JunboLuo Xuelai - Palmitoylation plays a crucial role in the development of cancer, but the causal relationship with oral cancer is still uncertain. The aim of this study was to describe the causal relationship between palmitoylation modified genes and oral cancer, while identifying intermediate factors. Genome-wide association studies of immune cells, oral cancer, and palmitoylation gene expression quantitative trait locus were derived from public databases. In this study, inverse variance weighting was used as the primary analytical method to investigate the causal relationship between exposure and outcome. In addition, this study uses Mendelian randomization (MR) Egger, simple mode, weighted median and weighted mode as supplementary analysis methods. To ensure the reliability of the findings, we further assessed horizontal pleiotropy and heterogeneity, and used the leave-one-out method to assess the stability of the MR results. Finally, mediated analysis was used to elucidate the potential mediated role of immune cell phenotype. Two-sample MR analysis revealed a causal relationship between palmitoylation genes and oral cancer. The results showed that zinc finger DHHC-type containing 19 (odds ratio [OR] = 0.6482, 95% CI: 0.5335-0.7875, P < .001) was negatively correlated with the occurrence of oral cancer. Zinc finger DHHC-type (ZDHHC)2 (OR = 1.6051, 95% CI: 1.3389-1.9242, P < .001) and ZDHHC24 (OR = 1.6077, 95% CI: 1.1588-2.2305, P = .0045) were positively correlated with oral cancer. The results of mediated MR analysis showed that CD28+ CD45RA+ CD8br absolute cell counts positively regulated ZDHHC2 and oral cancer (mediation effect [ME] = 0.0801; mediation proportion [MP] = 16.92%). CD28- CD8br absolute cell counts (ME = 0.0747; MP = 17.23%) and CD25 on IgD- CD38dim (ME = 0.0164; MP = 3.78%) positively modulated ZDHHC19- oral cancer. This study provides evidence supporting a causal relationship between palmitoylation genes and oral cancer, with immune cell phenotypes acting as mediators. Identifying a potential causal relationship between palmitoylation genes and oral cancer reveals its underlying mechanisms and suggests new therapeutic targets. - Source: PubMed
Jiang Zhong-HuiWei Yan-HongXie HangWang Hong-BingHe WeiWang Xin-Juan