Ask about this productRelated genes to: HDAC5 antibody
- Gene:
- HDAC5 NIH gene
- Name:
- histone deacetylase 5
- Previous symbol:
- -
- Synonyms:
- KIAA0600, NY-CO-9, FLJ90614
- Chromosome:
- 17q21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2016-10-06
Related products to: HDAC5 antibody
Related articles to: HDAC5 antibody
- Cells reprogram glycolysis pathway to cope with energy deficiency, in which the catalytic activity, stability, and noncanonical functions of glycolytic enzymes are finely regulated by posttranslational modifications (PTMs). Here, we report a metazoan-conserved dual degradation inhibition cascade whereby energy stress coordinates acetylation-phosphorylation crosstalk that simultaneously enhances glycolytic output and suppresses two protein degradation systems. Specifically, KAT2 (KAT2A)/HDACIIa (HDAC5)-mediated acetylation of PGK at K73 (PGK1; K75) antagonizes its ubiquitin-proteasomal degradation while strengthening its interaction with ALDO (ALDOA). Then, PGK exerts noncanonical kinase activity to phosphorylate ALDO at S272, thereby enhancing ALDO's substrate affinity and suppressing its chaperone-mediated autophagic-lysosomal degradation by inhibiting the interaction with HSC70 to simultaneously stabilize and activate ALDO to amplify glycolytic flux. This ancient survival axis underlies thermotolerance divergence in oysters and is hijacked in human lung adenocarcinoma to drive malignant proliferation. Our study integrates environmental adaptation and tumorigenesis through a unified metabolic signaling axis, broadening our understanding of PTM crosstalk in evolution and disease. - Source: PubMed
Publication date: 2026/08/18
Wang ChaogangDu MingyangLiu YutongWang JiafengJiang ZhuxiangQi HaigangWang WeiCong RihaoZhang GuofanLi Li - Post-traumatic sepsis is the leading cause of late mortality in intensive care units. While the concept of "gut-origin sepsis" has evolved over the past three decades, the stomach has largely been overlooked as an active contributor. This review synthesizes current evidence and proposes a novel "Gastrointestinal Axis" (GIA) integrating gastric and intestinal dysfunction as interconnected drivers of post-traumatic sepsis, with gastric autophagy as a proposed regulatory node. The mechanistic data supporting this framework derive primarily from intestinal epithelial cells and general sepsis models; direct evidence for gastric mucosal autophagy in human post-traumatic sepsis remains limited, and the causal inference that gastric autophagy failure initiates downstream intestinal injury remains a hypothesis requiring further validation. A comprehensive literature search of PubMed, Web of Science, and Scopus was conducted to identify relevant peer-reviewed studies on gut barrier dysfunction, dysbiosis, autophagy, and immune responses in post-traumatic sepsis. The central mechanistic framework involves histone deacetylase 5 (HDAC5) upregulation silencing ghrelin, thereby impairing gastric autophagy-a proposed regulatory node in the GIA-which reduces E2F1-mediated NF-κB suppression and impairs intestinal barrier integrity. Parallel protective pathways include PLK1-mTOR-regulated autophagy and SIRT3-mediated mitochondrial protection. This gastric dysfunction may propagate to the intestine, where dysbiosis with loss of obligate anaerobes and overgrowth of Enterobacteriaceae creates a "pathobiome" that potentially amplifies systemic inflammation. Bidirectional communication occurs via lymphatic, humoral, cellular, and neural routes. Emerging biomarkers such as intestinal fatty acid-binding protein, D-lactate, citrulline, and the Acute Gastrointestinal Injury grading system enable multimodal risk stratification. Early enteral nutrition (OR 0.36) and synbiotics (RR 0.61) show promise; preclinical data support HDAC5 inhibitors, ghrelin restoration, and teprenone as promising adjuncts for preserving GIA integrity. The GIA concept reframes gastric and intestinal protection as an integrated therapeutic strategy and provides a new conceptual foundation for preventing post-traumatic sepsis and guiding biomarker-driven mechanism-based interventions. - Source: PubMed
Publication date: 2026/07/17
Liu Xiang-YuLiu TianChai Jia-KeWu Yu-ShouLiu Hong-ShengQu Yi-RuiZhou HuiXu Cheng-FengChi Yun-Fei - Myofibroblasts are the cells responsible for collagen production, leading to tissue fibrosis. Because 20.5% of the total amino acids in collagen are proline, myofibroblasts must acquire a well-developed proline-producing mechanism during their differentiation. However, the detailed mechanism for myofibroblasts to acquire and keep the developed proline biosynthesis machinery remains obscure. Here, we show branched-chain amino acid transaminase 1 (Bcat1) is up-regulated in a substantial subset of Postn-expressing proto-myofibroblast-like fibroblasts, transitional cells en route to fully differentiated myofibroblasts, as well as in myofibroblasts in the fibrotic heart and liver of mice and humans and promotes the proline production. The branched-chain amino acid (BCAA) production by BCAT1 promotes SMAD3 phosphorylation via HDAC5 phosphorylation at Ser488, thereby enhancing SMAD3-dependent transcription of proline biosynthesis-related genes, Aldh18a1, Pycr1, and Eprs, in proto-myofibroblast-like fibroblasts and myofibroblasts. In BCAT1-deficient mice, expression of proline biosynthesis-related genes is significantly attenuated in their hearts after myocardial infarction, resulting in decreased cardiac fibrosis. Moreover, BCAT1 inhibitor treatment of mice with myocardial infarction reduces cardiac fibrosis. Our results identified a BCAT1-mediated pathway that promotes collagen production via proline biosynthesis regulation in proto-myofibroblast-like fibroblasts and myofibroblasts, which may provide a therapeutic target for cardiac fibrosis. - Source: PubMed
Publication date: 2026/07/16
Takizawa NoburoHironaka TakanoriWatanabe HayatoSuetsugu HarunaYoshioka KeisukeHorii YumaNagata YuriMatoba HiroakiKosako HidetakaHamase KenjiHirai GoNakaya Michio - The t(4;14) translocation is a high-risk cytogenetic abnormality in multiple myeloma (MM) that results in overexpression of fibroblast growth factor receptor 3 (FGFR3) and enhanced MM proliferation, leading to poor prognosis. Herein, we carried out a high-throughput screen on 1855 Food and Drug Administration (FDA)-approved pharmaceuticals and identified all-trans retinoic acid (ATRA), which alone has no anti-MM effect, as a potent drug that enhances the cytotoxic effects of immunomodulatory drugs (IMiDs) in t(4;14) MM cells. Mechanistically, ATRA activates retinoic acid receptor β (RARβ), which then binds to retinoic acid response elements in the FGFR3 promoter. IMiDs enhanced nuclear translocation of histone deacetylase (HDAC)-5 and 3 by reducing HDAC5 Ser498 phosphorylation levels. RARβ, HDAC5 and HDAC3 formed a co-repressor complex that reduced chromatin accessibility and H3K27 acetylation in FGFR3 promoter, FGFR3 expression, and suppressed phosphoinositide 3-kinase/AKT signaling pathways, leading to more MM cell death. Similarly, CD2314, a selective RARβ agonist, sensitized and resensitized t(4;14) MM cells to IMiDs in vitro and in vivo. Thus, these findings underscore the therapeutic potential of ATRA and RARβ agonists in enhancing the efficacy of IMiD-based treatments for t(4;14) MM and offer a promising strategy to overcome IMiD resistance and improve outcomes in this high-risk subgroup. - Source: PubMed
Publication date: 2026/07/30
Zhong LingWang QiangXian MiaoQian JianfeiZhang ChuanchaoWu WeiGuo QiZhang YufeiDuan RuiZu YouliMathur SunilOrlowski Robert ZZhan FenghuangYi Qing - 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