HDAC4
- Known as:
- HDAC4
- Catalog number:
- 000426A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- HDAC4
Related genes to: HDAC4
- Gene:
- HDAC4 NIH gene
- Name:
- histone deacetylase 4
- Previous symbol:
- BDMR
- Synonyms:
- KIAA0288, HDAC-A, HDACA, HD4, HA6116, HDAC-4
- Chromosome:
- 2q37.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2015-09-11
Related products to: HDAC4
Related articles to: HDAC4
- Heart failure (HF) is a systemic syndrome in which myocardial remodeling and multiorgan dysfunction exacerbate each other. This review focuses on the hepatokine Fetuin-A and the post-translational modification N-myristoylation in HF. Regarding Fetuin-A, we first demonstrated that circulating Fetuin-A levels were significantly lower in HF patients than in control subjects without structural heart disease. This reduction was associated with hepatic hypoperfusion. In a prospective study of 202 HF patients who underwent cardiopulmonary exercise testing, the combination of lower Fetuin-A and impaired exercise tolerance was independently associated with increased risk of cardiac events, suggesting that Fetuin-A could serve as a novel mediator of cardiac-hepatic-peripheral interaction. Regarding N-myristoylation, expression of N-myristoyltransferase 2 (NMT2) was significantly reduced in failing hearts. Cardiac-specific NMT2 knockdown exacerbated cardiac dysfunction, whereas AAV9-mediated NMT2 gene transfer attenuated cardiac remodeling and HF. Click chemistry-based proteomics identified MARCKS as a crucial substrate, and N-myristoylation of MARCKS prevented pathological hypertrophy by promoting its membrane localization, thereby suppressing CaMKII-HDAC4 signaling. These findings indicate that Fetuin-A and NMT2-dependent N-myristoylation play important roles in HF pathophysiology and represent potential novel therapeutic targets. - Source: PubMed
Publication date: 2026/08/13
Tomita YusukeMisaka TomofumiYokokawa TetsuroTakeishi Yasuchika - Co-evolution between viruses and autophagy has led to the emergence of viral strategies that manipulate host endoplasmic reticulum (ER) homeostasis, ultimately promoting viral replication. ER turnover is achieved through selective autophagy, also referred to as ER-phagy, which is regulated by the RETREG1/FAM134B (reticulophagy regulator 1) family of reticulon proteins. Nevertheless, how viruses target RETREG1, a receptor for ER-phagy, remains largely unclear. In this study, we demonstrate that infection with Senecavirus A (SVA), an emerging picornavirus, triggers the cleavage of RETREG1, which functions as a negative regulator of viral replication. By screening viral proteins, we identified the SVA 3C protease (3C[pro]) as the executor of this cleavage event. Detailed mapping revealed that residues Q428, E430, and G431 of RETREG1 are involved in its cleavage by the 3C[pro], and the resulting two fragments fail to suppress viral replication. Furthermore, proteolytic cleavage of RETREG1 by 3C[pro] impairs its ability to relieve ER stress and mediate ITPR1 degradation via RETREG1-dependent ER-phagy. This disruption leads to increased ER calcium (Ca) release and subsequent activation of autophagy through the CAMKK2-PRKAA2-MTOR axis, which ultimately facilitates SVA replication. Taken together, these findings indicate that SVA antagonizes the antiviral function of RETREG1-mediated ER-phagy via its 3C[pro], highlighting RETREG1 as a potential therapeutic target for combating SVA infection. 2-APB: 2-aminoethyl diphenylborinate; PRKAA2/AMPK: protein kinase AMP-activated catalytic subunit alpha 2; ATL3: atlastin GTPase 3; BHK-21: baby hamster kidney-21; CAMKK2: calcium/calmodulin dependent proteinkinase kinase2; CCPG1: cell cycle progression 1; CKAP4/CLIMP63: cytoskeleton associated protein 4; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DM: double mutant; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; eGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; GFP: green fluorescent protein; HSPA5/GRP78/BiP: heat shock protein family A (Hsp70) member 5; HA: hemagglutinin; HDAC4: histone deacetylase 4; HEK-293T: human embryonic kidney 293T; hpi: hours post-infection; IFA: indirect immunofluorescence assay; ITPR1/IP3R1: inositol 1,4,5-trisphosphate receptor type 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LIR: LC3-interacting region; mCherry: monomeric cherry; MTOR: mechanistic target of rapamycin kinase; REEP5: receptor accessory protein 5; RETREG1/FAM134B: reticulophagy regulator 1; RTN3: reticulon 3; SD: standard deviation; SEC61B: SEC61 translocon subunit beta; SEC62: SEC62 preprotein translocation factor; SERP1/RAMP4: stress associated endoplasmic reticulum protein 1; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; ST: swine testis; SVA: Senecavirus A; TEM: transmission electron microscopy; TEX264: testis expressed 264, ER-phagy receptor; Tm: tunicamycin; U2OS: human osteosarcoma epithelial cells; UV: ultraviolet; ZVAD-FMK: benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone; μg: microgram; μm: micrometer; μM: micromole. - Source: PubMed
Publication date: 2026/08/11
Mao JingyuYu JuZeng PenghuiYang XiaoyuShi YongyanQu YunjieZhou JianweiWang DedongSong JiangweiWang YongLiu JueHou Lei - Histone lactylation links lactate metabolism to chromatin regulation, but whether lactylation-program-associated transcriptional patterns delineate recurrent pan-cancer tumor states remains unclear. - Source: PubMed
Publication date: 2026/07/31
Bo ZhihaoZhang ShiyueZheng ZhiyuanMa JialuFeng YuankangLi JianqiaoLiu YangFu ZhinanXing HaotianYu ShuminGuo ShaominSi XianjingWang JiahaoWang RunpengWang RuiZhang XilingYue DanWang Yong - Arteriovenous fistula (AVF) maturation is characterized by outward remodeling presented mainly as wall thickening and lumen enlargement, probably mediated by increased differentiated vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) deposits, at least in part. Our previous study revealed that the highly conserved transcription factor early growth response protein 2 (EGR2) promoted renal tubular epithelial cell differentiation and ECM accumulation. Here, we found that EGR2 expression was enhanced in venous outflow tracts from end-stage renal disease (ESRD) patients and mice with AVF surgery accompanied by a thickened venous wall and enlarged lumen. Then, the knockdown of EGR2 could inhibit AVF maturation while EGR2 overexpression further promoted outward remodeling in AVF mice with adeno-associated virus (AAV) administration regulated by differentiated VSMCs and ECM deposition. Mechanistically, gene deletion of EGR2 inhibited c-Myc possibly by binding to the promoter region of the insulin-like growth factor 2 binding protein 2 (IGF2BP2) gene. Moreover, EGR2 was upregulated by histone deacetylase 4 (HDAC4) which probably negatively regulated transcription factor c-Jun, the latter was reported to antagonize the effect of EGR2. Thus, we speculated that EGR2 is upregulated by HDAC4 possibly by negatively regulating c-Jun and promoting outward remodeling through the IGF2BP2/ c-Myc signaling axis during AVF maturation. - Source: PubMed
Publication date: 2026/07/29
Song AnniYan RuiweiHuang MingyuZou XingjianGao PanCai ChuanqiYin XingjieLuo PengliZhu PingZhang Chun - Inspired by reports that HDAC blockade can trigger compensatory activation of the LIFR-JAK1-STAT3 axis in solid tumors, we designed and synthesized a series of niclosamide-based STAT3/HDAC dual-target inhibitor candidates by incorporating a SAHA-derived hydroxamate zinc-binding group into the pleiotropic, STAT3-modulating niclosamide scaffold. Biological evaluation identified NS06 as the best-balanced analogue, with IC values of 1.49 and 1.41 μM against MDA-MB-231 and HCT116 cells, respectively. Mechanistic studies showed that NS06 bound STAT3 in vitro (SPR, K = 5.82 μM), suppressed STAT3 phosphorylation, and inhibited HDAC1, HDAC3, and HDAC6 with IC values of 129.1, 451.2, and 230.4 nM, respectively, while showing limited inhibition of HDAC4 and HDAC11 in the primary screen. NS06 also increased histone H3 acetylation, induced apoptosis, and inhibited migration and colony formation. In addition, NS06 retained antiproliferative activity in a 3D tumor spheroid model and showed improved Caco-2 permeability together with moderate liver microsomal stability (t ≈ 48.6 min in rat liver microsomes). Docking and 100-ns molecular dynamics simulations further supported chemically plausible binding modes in the HDAC1 catalytic pocket and the STAT3 SH2 domain. Overall, these findings support niclosamide as a tractable scaffold for mechanism-driven STAT3/HDAC dual-target inhibitor design and identify NS06 as a promising lead for further optimization against solid tumors. - Source: PubMed
Publication date: 2026/07/25
Shi YuchenZhang QihaoWang ChenxiLu ZipengChen FangfangHan LiuXu ZhouyangZhang YuanMa ShumeiYe FaqingWang Xuebao