BRD4 (49-460), His, Human Proteins
- Known as:
- BRD4 (49-460), histidine, Human Proteins
- Catalog number:
- Z03187-100
- Product Quantity:
- 100ug
- Category:
- Proteins
- Supplier:
- Genscript
- Gene target:
- BRD4 (49-460) His Human Proteins
Related genes to: BRD4 (49-460), His, Human Proteins
- Gene:
- BRD4 NIH gene
- Name:
- bromodomain containing 4
- Previous symbol:
- -
- Synonyms:
- HUNKI, MCAP, CAP, HUNK1
- Chromosome:
- 19p13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-26
- Date modifiied:
- 2015-09-11
Related products to: BRD4 (49-460), His, Human Proteins
Related articles to: BRD4 (49-460), His, Human Proteins
- Bromodomains are conserved acetyl-lysine reader domains that play a central role in the assembly of transcriptional regulatory complexes. While generally presumed to function as monomers, bromodomain homo-dimers have been identified, and several bromodomain-containing proteins have been linked to biomolecular condensates, where locally elevated concentrations may promote dimerization. Here, we investigated bromodomain dimerization with an integrated approach that combines structural and biophysical measurements with AlphaFold-based predictions across the bromodomain family. Using the second bromodomain (BD2) of BRD4 as a model system, we characterized the thermodynamics and kinetics of its monomer-dimer equilibrium by two-dimensional nuclear magnetic resonance (NMR) lineshape analysis and CPMG relaxation dispersion. We found that the BRD4 dimer forms transiently with a dissociation constant near 400 μM and a lifetime near 1 ms. Using our NMR-derived restraints, we performed data-driven docking to generate models of the BRD4 dimer. To assess dimerization propensity across the wider bromodomain family, we leveraged AlphaFold-Multimer and AlphaFold3 to systematically predict homo-dimeric models for all human bromodomains. We identified several predicted dimer architectures, with 15 bromodomain dimers that have higher interface-confidence scores than BRD4. Overall, our results suggest that weak and reversible dimerization may be more widespread among bromodomains, where it could contribute to function in dynamic transcriptional assemblies. - Source: PubMed
Publication date: 2026/05/22
Dengler Alisa SLunglmeir LaraBrandl Matthias JAlderson T Reid - To investigate the effects of hesperidin on adipogenesis and the ROS/JNK/BRD4/SHP2 signaling pathway in High-Fat Diet (HFD)-induced obese rats, and to explore the potential mechanisms by which hesperidin promotes white adipose browning in obese rats. We obtained high-throughput sequencing datasets of normal-weight individuals and obese patients from the GEO database and performed bioinformatics analysis. Functional enrichment analysis, cell trajectory analysis, and intercellular communication analysis were conducted on the single-cell transcriptome sequencing data (GSM9012222, GSM9024554, GSM9012223, GSM9024555). Thirty-six male SD rats, aged six weeks, were split into two groups at random: a sham group (n = 9) and an obesity modelling group (n = 27). A diet-induced obesity model was established by feeding the rats a high-fat diet. After 12 weeks, the successfully modeled rats were randomly divided into a Model group, a Hesperidin group, and a Hesperidin+PHPS1 group, with 9 rats in each group. Following the intervention period, body weight and Lee's index were measured, and the weights of inguinal, epididymal, and perirenal white adipose tissue (WAT), as well as interscapular brown adipose tissue (BAT), were compared among the groups. The levels of malondialdehyde (MDA), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in serum and inguinal adipose tissue were measured using assay kits. Glucose homeostasis was assessed via oral glucose tolerance test (OGTT) and insulin tolerance test (ITT), which measured blood glucose levels at predefined time points. Hematoxylin-eosin (HE) staining was performed on rat inguinal white adipose tissue (iWAT). Quantitative real-time PCR (RT-qPCR) was applied to quantify the mRNA abundance of key browning-associated markers, including UCP1, PRDM16 and PGC1α. Protein expression levels were quantified via Western blot. Western blot was used to identify protein expression when 3T3-L1 cells were exposed to various stimuli in vitro. Mitochondrial membrane potential was evaluated with the JC-1 assay. Oil Red O staining was performed to visualize lipid droplets in cells. In addition, to investigate whether PHPS1 exerts effects on the rat liver, two additional rat groups were established: the control group and the PHPS1 group, with 6 rats in each group. The mRNA expression level of SHP2 was determined by RT-qPCR, and the serum activities of ALT and AST in rats were measured using corresponding assay kits. In vivo experiments showed that compared with the sham group, the model group showed increased body weight, masses of inguinal, epididymal, and perirenal WAT, serum MDA levels, and expression of NOX4, p-BRD4, PPARγ, and C/EBPα, while the mass of interscapular BAT, SOD and GPX levels in serum and adipose tissue, SOD and GPX levels, and p-SHP2 expression were decreased. The expression levels of UCP1, PRDM16 and PGC1α were downregulated. Fasting blood glucose and the area under the curve (AUC) were elevated. Meanwhile, the cell area of inguinal adipose tissue was significantly increased. Compared with the model group, Hesperidin significantly improved the above lipid metabolism, white adipose browning indicators andoxidative stress. However, PHPS1 inhibited the ameliorative effects of hesperidin on obese rats. Furthermore, PHPS1 can effectively inhibit SHP2 without exerting metabolic effects on the liver. In vitro experiments showed that hesperidin also suppressed the expression of NOX4, p-JNK, p-BRD4, PPARγ and SREBP1C, improved impaired mitochondrial function, and reduced intracellular lipid droplet formation. Bioinformatics analysis, together with in vivo and in vitro experiments, demonstrated that hesperidin inhibits high-fat diet-induced obesity by regulating the ROS/JNK/BRD4/SHP2 signaling pathway. Hesperidin inhibits HFD-induced obesity by regulating ROS/JNK/BRD4/SHP2 signaling-induced adipogenesis. - Source: PubMed
Publication date: 2026/06/25
Xie QiZhang ShaohuaZhao JinWang LinaChang YupingGuo DandanCheng LinglingZhou Tengteng - Genomic instability in high-grade serous tubo-ovarian carcinoma (HGSTOC) can generate fusion genes with potential roles in tumor evolution and clinical relevance. HGSTOCs commonly disseminate prior to diagnosis, but most studies analyze only one tumor sample per patient, limiting understanding of fusion gene dynamics. Here, RNA sequencing was performed on 108 tumor samples from multiple intra‑abdominal sites in 23 patients. A consensus approach involving three fusion callers identified 170 high-confidence fusion genes present in all samples from each patient, most of which were non‑recurrent and not in-frame. Protein kinases were significantly enriched among fusion partners, and commonly retained intact catalytic domains. Several of the kinase fusion genes may have oncogenic relevance, including AKAP8L::BRD4 (recurrent in three patients), GPBP1L1::MKNK1, SPAG16::ERBB4, UGP2::MAPK4, and STRN3::PRKD1. Four fusions involved homologous recombination-related genes, including FUT10::SPIDR, RAD54B::VIRMA, RAD54L::PLXNA2, and SMARCAD1::BOD1L1. Integration of these fusion genes with other somatic alterations in homologous recombination-related genes, deficiency signatures, and germline BRCA1/2 variants increased the involvement of the homologous recombination pathway to 15 HGSTOCs (65%). Overall, HGSTOC has a heterogeneous fusion gene landscape, and multi-site sampling with consensus calling offers a robust strategy for resolving fusion profiles. - Source: PubMed
Publication date: 2026/06/25
Panagopoulos IoannisStranger AneSveen AnitaJareid MieKidd Susanne GBischof KatharinaTaskén KjetilDørum AnneDavidson BenLothe Ragnhild ASkotheim Rolf IJohannessen Bjarne - The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC) development and therapeutic responses, including to genotoxic agents. While epigenetic modulators have been shown to contribute to the DDR, how chromatin regulation dictates responses to DNA damage in PDAC remains incompletely understood. Here, we identify Class I histone deacetylases (HDACs) as critical regulators of the DDR. HDAC1/2 direct the genomic distribution of H3K27ac, ensuring sufficient BRD4 and RNA polymerase II (Pol II) occupancy at DDR gene promoters. HDAC inhibition by entinostat shifts the balance of H3K27 acetylation preferentially toward intergenic regions, diverting BRD4 and Pol II from promoters, thereby suppressing DDR gene expression. In line with this, HDAC inhibition heightens DNA damage and sensitizes PDAC to diverse DNA-damaging and DDR-targeting agents. Since the clinical development of HDAC inhibitors has been limited by systemic toxicity, we developed bottlebrush prodrug (BPD) nanoparticles for tumor-selective entinostat delivery. Entinostat-BPD achieved tumor-specific HDAC inhibition while displaying potent efficacy and reduced systemic toxicity. These findings reveal an HDAC-dependent DDR vulnerability and offer combinational and precision targeting strategies to facilitate clinical translation and improve PDAC patient outcomes. - Source: PubMed
Publication date: 2026/06/25
Liang GaoyangNguyen Hung V-TZhu JonathanTiriac HervéZafar HadiqaCao Daniel YEstepa GabrielaNelson Dylan CDai YangOh Tae GyuLiddle ChristopherYu Ruth THunter TonyEngle DannielleShaw ReubenLowy Andrew MFan WeiweiTruitt Morgan LAtkins Annette RJohnson Jeremiah ADownes MichaelEvans Ronald M - Idiopathic pulmonary fibrosis (IPF) is sustained by a self-amplifying pathological circuit involving senescence-associated epithelial injury and fibroblast activation, which together drive persistent inflammatory signaling, excessive extracellular matrix deposition, and progressive loss of lung function. Although proteolysis-targeting chimeras (PROTACs) offer a powerful approach to eliminate disease-driving proteins, their application in fibrotic lung disease remains limited by inefficient pulmonary delivery, poor lesion retention, and insufficient intervention in multicellular profibrotic networks. Herein, we develop an inhalable enzyme-activated polymeric PROTAC nanococktail that enables concurrent degradation of two key profibrotic signaling regulators in fibrotic lungs. The nanococktail consists of GAL@SD and FAP@BD, two disease-microenvironment-responsive nanoparticles carrying distinct PROTAC cargos. GAL@SD responds to elevated senescence-associated β-galactosidase activity in fibrotic lungs and releases a stimulator of interferon genes (STING)-degrading PROTACs to suppress senescence-associated inflammatory signaling linked to impaired alveolar epithelial repair. FAP@BD is activated by fibroblast activation protein-α enriched in activated fibroblast-dominated fibrotic regions, delivering a bromodomain-containing protein 4 (BRD4)-degrading PROTAC to inhibit myofibroblast activation and extracellular matrix production. After inhalation, both nanoparticles exhibit efficient mucus penetration, improved pulmonary retention, and preferential accumulation in fibrotic lesions, enabling localized degradation of STING and BRD4. In a bleomycin-induced mouse model of pulmonary fibrosis, the combined PROTAC nanococktail achieves superior therapeutic efficacy compared with either single PROTAC nanoparticle, as demonstrated by restored lung architecture, improved respiratory function, reduced collagen deposition, and reversal of fibrosis-associated transcriptional programs. These results demonstrate an inhaled dual-PROTAC nanotherapeutic strategy for simultaneously attenuating epithelial senescence-associated inflammation and fibroblast-driven matrix remodeling. - Source: PubMed
Publication date: 2026/06/24
Tan QiaolingZhao YandongZhang YangningChen HaoXu ZhiqiPan ZhenhaiEl-Khouly Mohamed EYuan Youyong