AHSA1 polyclonal antibody
- Known as:
- AHSA1 pab (anti-)
- Catalog number:
- PAB9927
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Abno
- Gene target:
- AHSA1 polyclonal antibody
Related genes to: AHSA1 polyclonal antibody
- Gene:
- AHSA1 NIH gene
- Name:
- activator of HSP90 ATPase activity 1
- Previous symbol:
- C14orf3
- Synonyms:
- p38, Aha1, hAha1
- Chromosome:
- 14q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-01
- Date modifiied:
- 2016-11-23
Related products to: AHSA1 polyclonal antibody
Related articles to: AHSA1 polyclonal antibody
- With the acceleration of global population aging, the progressive deterioration of cardiac structure and function has become a critical determinant of cardiovascular health, presenting a significant public health challenge. Checkpoint kinase 1 (CHK1), a key cell cycle checkpoint protein, plays an essential role in various biological processes by mediating signaling cascades. While CHK1 has been shown to be important for heart regeneration, its role in the aging process of the heart remains unclear. In this study, we investigated the alterations in CHK1 expression in aging hearts and elucidated the underlying regulatory mechanisms. In both in vivo and in vitro models, CHK1 expression was significantly downregulated during aging. To assess its functional role, we generated cardiomyocyte-specific CHK1 overexpression and knockout mice and compared their cardiac performance. We found that CHK1 overexpression alleviated age-associated cardiac dysfunction, while CHK1 knockout worsened cardiac function in aged mice. Furthermore, CHK1 overexpression significantly attenuated doxorubicin (DOX)-induced acutely senescence in adult mouse cardiomyocytes (AMCMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Mechanistic studies revealed that CHK1 overexpression delayed cardiac aging by activating heat shock protein 90 (HSP90)-mediated mitophagy. Immunoprecipitation and mass spectrometry (IP-MS) analyses demonstrated that CHK1 directly interacts with the activator of HSP90 ATPase homolog 1 (AHSA1), thereby suppressing TRIM8-mediated ubiquitination and degradation, facilitating AHSA1-HSP90 complex formation, and enhancing HSP90 ATPase activity. Overall, our results suggest that CHK1 overexpression activates mitophagy via the AHSA1-HSP90 pathway to mitigate cardiac aging. This study highlights the critical role of CHK1 in cardiac aging and proposes a potential therapeutic strategy for aging-associated cardiomyopathy and heart failure. - Source: PubMed
Publication date: 2026/05/30
Jing PengZhou Liu-HuaChen Shu-XuanChen Jia-YiGu Ling-FengYang Tong-TongWang Si-BoDu ChongChen Yi-XiWang Qi-MingWang Lian-ShengWang Hao - Hsp90 is a dimeric molecular chaperone essential for the maturation, activation, stabilization, and folding of numerous clients required for cellular functions. Hsp90 progresses through a dynamic ATP-driven conformational cycle that is precisely regulated by accessory proteins known as co-chaperones. Here, we show that the isolated N-domain of Aha1 (Aha1N156) binds the apo state of Hsp90 but fails to associate with the closed, nucleotide-bound state. In contrast, the full-length Aha1 binds Hsp90 in both conformational states, suggesting a key role for the Aha1 C domain in binding to the nucleotide-bound, closed state of Hsp90. Surprisingly, the Aha1 paralogue Hch1, which corresponds to the Aha1 N domain, was capable of binding to Hsp90 in both the apo and nucleotide-bound states. Interestingly, the addition of a 14 amino acid residues section of the linker to the Aha1 N domain restores closed-state binding, indicating an unexpected role for the linker in stabilizing nucleotide-dependent interactions. Analysis of yeast-human Aha1 chimeras further demonstrates that the C-terminal domain of Aha-type co-chaperones serves as an evolutionarily conserved anchoring module, enabling stable engagement of the ATP-bound state despite significant sequence divergence. This work allows us to propose a model in which the Aha1 C domain allows for the repositioning of the Aha1 N domain that occurs during the transition from the apo to the ATP-bound state of Hsp90. - Source: PubMed
Publication date: 2026/04/21
Amoah Desmond PrahBhat RakeshTrad MalakHussein Solomon KOverduin MichaelLaPointe Paul - Endometrial cancer (EC) is a malignant neoplasm with a high prevalence, posing a significant threat to women's health and a substantial burden on the healthcare system. The endoplasmic reticulum-associated degradation (ERAD) pathway is essential for sustaining cellular homeostasis and tumorigenesis. This study elucidated the mechanisms of the DnaJ Heat Shock Protein Family (Hsp40) Member B4 (DNAJB4) and the activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) in EC cells. DNAJB4 was knocked down in Ishikawa cells, and its impact on cellular biological functions was assessed using colony formation assays, flow cytometry, and western blot. The association between AHSA1 and DNAJB4 was identified using the Co-Immunoprecipitation (Co-IP) method. Ishikawa and RL95-2 cells overexpressing AHSA1 were generated, followed by functional assays and analysis of associated protein expressions. The knockdown of DNAJB4 markedly impeded the colony formation of Ishikawa and RL95-2 cells, enhanced apoptosis, and elevated the expressions of critical ERAD proteins X-box binding protein 1 (XBP-1s), activating transcription factor 4 (ATF4), C/EBP-homologous protein (CHOP), and growth arrest and DNA damage-inducible protein 34 (GADD34). AHSA1 bound to DNAJB4. The overexpression of AHSA1 enhanced the production of the DNAJB4 protein, facilitated cell colony formation, diminished cell apoptosis, and suppressed the expressions of ERAD-related proteins; however, the deletion of DNAJB4 negated these effects of AHSA1 overexpression. Collectively, AHSA1 and DNAJB4 cooperatively maintain efficient ERAD function, thereby alleviating endoplasmic reticulum stress and promoting EC progression. - Source: PubMed
Publication date: 2026/04/09
Ye ZhongxueYu ChenCao SiyuJiang Yafen - Advances in RNA interference technology have established it as a powerful therapeutic tool with important future potential. The design and the chemical modifications of the siRNA nucleotide backbone have greatly enhanced stability, durability, and pharmacokinetics while minimizing tolerability risks. The optimal combination of these modifications depends on the target gene, tissue, and RNA sequence, necessitating an iterative, experimental approach that currently relies heavily on animal models. To reduce the reliance and number of (humanized) animals required, we developed a human long-term liver 3D spheroid model designed for screening GalNAc-conjugated siRNAs which captures the process of uptake, potency, and durability for early in vitro screening. These liver spheroids remain viable in culture for at least 5 weeks while maintaining expression of the asialoglycoprotein receptor to facilitate GalNAc mediated uptake. siRNA was efficiently internalized by the spheroids without the need for transfection reagents, and its durable silencing efficiency was assessed by monitoring AHSA1 target gene expression over time. Target gene silencing in the spheroid model persisted up to 5 weeks post-treatment. Fluorescently labeled siRNA enabled visualization of uptake and distribution within the spheroid, revealing somewhat reduced siRNA accumulation in pericentral CYP3A4+ hepatocytes accompanied with somewhat reduced ASGR1 expression. No signs of hepatotoxicity were observed under the conditions used. By varying the number of phosphorothioate modifications in the siRNA backbone, distinct differences in silencing efficiency and durability were observed which were principally similar as obtained in vivo in mice. We propose that this long-term human liver spheroid model provides a valuable preclinical platform for evaluating siRNA-based therapeutics with respect to uptake, durability, and silencing efficiency, and could refine early in vitro screening and accelerate drug development. - Source: PubMed
Scholten Gijs-JanGrundmann ClaraNordling ÅsaCoskun CarolineEngelhardt VolkerSadhasivam LingheswarEinfalt TomažIngelman-Sundberg Magnusvan Riet Sander - Recent structure-activity relationship (SAR) studies identified multiple Hsp90/Aha1 small molecule disruptors that manifest moderately improved potencies and physiochemical properties. Among these molecules, a 1,5-bisubstituted-1,2,3-triazole containing molecule (Triazole A), demonstrated the importance of a cis-amide bond. Consequently, this work aimed to optimize Triazole A via a nitrogen scan and Topliss tree approach. The potency was determined against cell lysates and co-Immunoprecipitation (co-IP) experiments. The most efficacious molecules were evaluated for physiochemical properties that include aqueous solubility, human liver microsome half-life, and MDCK-MDR1 permeability. New molecules emerged from this study that manifest nanomolar potency and improved activity in cell-based co-IP experiments. These new molecules represent a significant improvement over prior Hsp90/Aha1 disruptors and provide chemical tools to investigate the significance of Hsp90/Aha1 complexes. - Source: PubMed
Publication date: 2026/02/02
Catalfano Kevin CRakonick Margaret HBlagg Brian S J