更新于：2024-11-01

ASK1 x DAB2IP

更新于：2024-11-01

基本信息

关联

项与 ASK1 x DAB2IP 相关的药物

GLPG-3535

靶点

ASK1 x DAB2IP

作用机制

ASK1抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ASK1 x DAB2IP 相关的临床结果

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100 项与 ASK1 x DAB2IP 相关的转化医学

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0 项与 ASK1 x DAB2IP 相关的专利（医药）

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项与 ASK1 x DAB2IP 相关的文献（医药）

2022-12-01·BMC Cancer2区 · 医学

DAB2IP down-regulates HSP90AA1 to inhibit the malignant biological behaviors of colorectal cancer

2区 · 医学

ArticleOA

作者: Liu, Lan ; Yang, Zhenwei ; Xu, Cong ; Liu, Jing ; Wu, Jixiong ; Peng, Yanan ; Zhang, Mengna ; Wang, Hongling ; Zhao, Qiu ; Zhang, Hailin

AbstractBackgroundStudies have shown that DAB2IP inhibits cancer progression, while HSP90AA1 promotes cancer progression. However, the specific regulatory mechanism of DAB2IP and HSP90AA1 in colorectal cancer (CRC) is not clear. Our aim is to investigate the role and mechanism of DAB2IP and HSP90AA1 in the development of CRC.MethodsWe used bioinformation to analyze the interaction between DAB2IP and HSP90AA1 and predict their downstream pathways. Then, a series of in vitro and in vivo experiments were conducted to reveal the role of DAB2IP and HSP90AA1 in the invasion and metastasis of colorectal cancer, and flow cytometry was used to explore their effects on apoptosis.ResultsLoss of DAB2IP was associated with poor prognosis of CRC. In contrast, elevated expression of HSP90AA1 was associated with the malignant behavior of CRC. The present study demonstrated a negative correlation between DAB2IP and HSP90AA1. Using bioinformatic analysis, we scanned SRP9 which was highly expressed in CRC, as a co-related gene of DAB2IP and HSP90AA1. Mechanistically, DAB2IP promoted apoptosis through HSP90AA1/SRP9/ASK1/JNK signaling axis in CRC.ConclusionsThese findings provide evidence that DAB2IP-based therapy may enhance the anticancer effect of HSP90AA1 inhibitors, and combined targeting of DAB2IP and HSP90AA1 may be a powerful treatment strategy to combat CRC.

2021-01-01·Cell Proliferation2区 · 生物学

MicroRNA‐146b‐5p overexpression attenuates premature ovarian failure in mice by inhibiting the Dab2ip/Ask1/p38‐Mapk pathway and γH2A.X phosphorylation

2区 · 生物学

ArticleOA

作者: Dou, Fangfang ; Gong, Zhangbin ; Nie, Xiaoli ; Chen, Jiulin ; Chen, Chuan ; Liu, Te ; Wang, Zhenxin ; Lin, Jiajia

AbstractObjectiveTo examine the role of high‐fat and high‐sugar (HFHS) diet‐induced oxidative stress, which is a risk factor for various diseases, in premature ovarian failure (POF).Materials and methodsOvarian granulosa cells (OGCs) were isolated from mice and cultured in medium supplemented with HFHS and poly (lactic‐co‐glycolic acid) (PLGA)‐cross‐linked miR‐146b‐5p nanoparticles (miR‐146@PLGA). RNA and protein expression levels were examined using quantitative real‐time polymerase chain reaction and Western blotting, respectively. HFHS diet‐induced POF model mice were administered miR‐146@PLGA.ResultsThe ovarian tissue of mice fed a HFHS diet exhibited the typical pathological characteristics of POF. HFHS supplementation induced oxidative stress injury in the mouse OGCs, activation of the Dab2ip/Ask1/p38‐Mapk signalling pathway and phosphorylation of γH2A.X in vitro and in vivo. The results of the luciferase reporter assay revealed that miR‐146 specifically downregulated p38‐Mapk14 expression. Meanwhile, co‐immunoprecipitation and Western blot analyses revealed that HFHS supplementation upregulated nuclear p38‐Mapk14 expression and consequently enhanced γH2A.X (Ser139) phosphorylation. The HFHS diet‐induced POF mouse model treated with miR‐146@PLGA exhibited downregulated p38‐Mapk14 expression in the OGCs, mitigated OGC ageing and alleviated the symptoms of POF.ConclusionsThis study demonstrated that HFHS supplementation activates the Dab2ip/Ask1/p38‐Mapk signalling pathway and promotes γH2A.X phosphorylation by inhibiting the expression of endogenous miR‐146b‐5p, which results in OGC ageing and POF development.

2020-01-01·Arteriosclerosis, Thrombosis, and Vascular Biology1区 · 医学

Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction

1区 · 医学

Article

作者: Li, Zheng ; Ji, Weidong ; Min, Wang ; Zhang, Haifeng ; Zhou, Huanjiao Jenny ; Li, Li

Objective: Vascular endothelial cells (ECs) normally maintain vascular homeostasis and are regulated by proinflammatory cytokines and reactive oxygen species. A human genome-wide association study identified that AIP1 (ASK1 [apoptosis signal-regulating kinase 1]-interacting protein-1; also identified as DAB2IP ) gene variants confer susceptibility to cardiovascular disease, but the underlying mechanism is unknown. Approach and Results:We detected a normal AIP1 form (named AIP1A) in the healthy aorta, but a shorter form of AIP1 (named AIP1B) was found in diseased aortae that contained atherosclerotic plaques and graft arteriosclerosis. AIP1B transcription in resting ECs was suppressed through epigenetic inhibition by RIF1 (Rap1 [ras-related protein 1]-interacting factor 1)/H3K9 (histone H3 lysine 9) methyltransferase-mediated H3K9 trimethylation, and this inhibition was released by proinflammatory cytokines. AIP1A, but not AIP1B, was downregulated by proteolytic degradation through a Smurf1 (SMAD [suppressor of mothers against decapentaplegic miscellaneous] ubiquitylation regulatory factor 1)-dependent pathway in ECs under inflammation. Therefore, AIP1B was the major form present during inflammatory conditions. AIP1B, which lacks the N-terminal pleckstrin homology domain of AIP1A, localized to the mitochondria and augmented TNFα (tumor necrosis factor alpha)-induced mitochondrial reactive oxygen species generation and EC activation. AIP1B-ECTG (EC-specific AIP1B transgenic) mice exhibited augmented reactive oxygen species production, EC activation, and neointima formation in vascular remodeling models.Conclusions:Our current study suggests that a shift from anti-inflammatory AIP1A to proinflammatory AIP1B during chronic inflammation plays a key role in inflammatory vascular diseases.