KPNA1

更新于：2025-01-23

基本信息

别名

Importin subunit alpha-5、Importin subunit alpha-5, N-terminally processed、IPOA5

+ [9]

简介

Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

关联

100 项与 KPNA1 相关的临床结果

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100 项与 KPNA1 相关的转化医学

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0 项与 KPNA1 相关的专利（医药）

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167

项与 KPNA1 相关的文献（医药）

2024-12-01·Journal of Pediatric Genetics

Microdeletion 3q13.33-3q21.2: A Rare Cause of Neurodevelopmental Disorder

Article

作者: Huang, Yi Juan ; Fan, Mei Qiong ; Zhou, Liang Ji ; Chen, Maofa ; Chen, Yuan Qiu ; Gou, Chen Yu ; Gao, Yu ; Jia, Rong Pu ; Lin, Hua Ming ; Li, Si

AbstractChromosomal sub-microscopic imbalances, such as microdeletions and microduplications, are associated with multiple genetic disorders. Here, we illustrate microdeletion 3q13.33q21.2 might be responsible for neurodevelopmental disorder in two patients.There are two patients with neurodevelopmental disorder in a family of seven. We used chromosomal microarray analysis to identify the microdeletion 3q13.33q21.2. Next-generation sequencing was utilized to exclude the presence of allelic mutations within the microdeletion region 3q13.33q21.2, which may have a potential role in the development of disease in patients affected with secondary genetic alterations.Patient 4 was diagnosed with dilated left third ventricle, neurodevelopmental disorder, and mild abnormalities in electroencephalogram through a series of clinical examinations. Patient 6 was diagnosed with attention deficit hyperactivity disorder, short stature, intellectual disability, and concurrent epilepsy. By investigating the 3q13.33q21.2 band of the University of California, Santa Cruz database, we screened out the genes related to developmental delay and intellectual disability, including ADCY5 SEMA5B andKPNA1, which were highly suspected to be related to intelligence. This region also involves CASR, a gene that has been reported to be associated with epilepsy.The ADCY5 and SEMA5B genes may be key genes to cause neurodevelopmental disorder. Abnormal expression of the CASR gene may lead to the occurrence of epilepsy.

2024-10-01·Advanced Science

MAPK Signaling‐Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin‐Induced Apoptosis and Ferroptosis

Article

作者: Wang, Ziyang ; Wen, Xiangqiong ; He, Weiling ; Zhang, Xiang ; Di, Yuqin ; Qin, Jiale ; Ye, Lvlan ; Song, Mei ; Wang, Youpeng

AbstractChemotherapy resistance remains a major challenge in the treatment of colorectal cancer (CRC). Therefore, it is crucial to develop novel strategies to sensitize cancer cells to chemotherapy. Here, the fringe family is screened to determine their contribution to chemotherapy resistance in CRC. It is found that RFNG depletion significantly sensitizes cancer cells to oxaliplatin treatment. Mechanistically, chemotherapy‐activated MAPK signaling induces ERK to phosphorylate RFNG Ser255 residue. Phosphorylated RFNG S255 (pS255) interacts with the nuclear importin proteins KPNA1/importin‐α1 and KPNB1/importin‐β1, leading to its translocation into the nucleus where it targets p53 and inhibits its phosphorylation by competitively inhibiting the binding of CHK2 to p53. Consequently, the expression of CDKN1A is decreased and that of SLC7A11 is increased, leading to the inhibition of apoptosis and ferroptosis. In contrast, phosphor‐deficient RFNG S225A mutant showed increased apoptosis and ferroptosis, and exhibited a notable response to oxaliplatin chemotherapy both in vitro and in vivo. It is further revealed that patients with low RFNG pS255 exhibited significant sensitivity to oxaliplatin in a patient‐derived xenograft (PDX) model. These findings highlight the crosstalk between the MAPK and p53 signaling pathways through RFNG, which mediates oxaliplatin resistance in CRC. Additionally, this study provides guidance for oxaliplatin treatment of CRC patients.

2023-10-31·Journal of virology

Seneca Valley virus 3C^pro antagonizes type I interferon response by targeting STAT1-STAT2-IRF9 and KPNA1 signals.

Article

作者: Song, Jiangwei ; Wang, Dan ; Quan, Rong ; Liu, Jue ; Wang, Jing ; Guo, Yitong

IMPORTANCEType I interferon (IFN) signaling plays a principal role in host innate immune responses against invading viruses. Viruses have evolved diverse mechanisms that target the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway to modulate IFN response negatively. Seneca Valley virus (SVV), an emerging porcine picornavirus, has received great interest recently because it poses a great threat to the global pork industry. However, the molecular mechanism by which SVV evades host innate immunity remains incompletely clear. Our results revealed that SVV proteinase (3C^pro) antagonizes IFN signaling by degrading STAT1, STAT2, and IRF9, and cleaving STAT2 to escape host immunity. SVV 3C^pro also degrades karyopherin 1 to block IFN-stimulated gene factor 3 nuclear translocation. Our results reveal a novel molecular mechanism by which SVV 3C^pro antagonizes the type I IFN response pathway by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which has important implications for our understanding of SVV-evaded host innate immune responses.

项与 KPNA1 相关的新闻（医药）

2024-08-02

·生物谷

Front Immunol：新研究揭示呼吸道合胞病毒抑制人体免疫反应机制，并为药物开发提供一个有希望的新靶点

研究人员发现了危险的呼吸道合胞病毒如何消除我们的免疫反应，并由此为药物开发人员找到了一个令人兴奋的新靶点。呼吸道合胞病毒（respiratory syncytial virus, RSV）在全球人口中造成了严重的疾病负担，估计每年有 3310 万病例，是导致婴儿支气管炎和病毒性肺炎的主要原因。它对儿童和老年人的影响尤其严重，治疗方案有限，而且效果相对较差。欧洲最近批准了一些 RSV 疫苗，但是爱尔兰卫生服务署目前尚未提供此类疫苗。在一项新的研究中，来自爱尔兰都柏林三一学院的研究人员发现了危险的RSV如何消除我们的免疫反应，并由此为药物开发人员找到了一个令人兴奋的新靶点。相关研究结果发表在2024年6月13日的Frontiers in Immunology期刊上，论文标题为“Respiratory syncytial virus NS1 inhibits anti-viral Interferon-α-induced JAK/STAT signaling, by limiting the nuclear translocation of STAT1”。论文通讯作者为都柏林三一学院生物化学与免疫学学院病毒学免疫学助理教授Nigel Stevenson。这些作者利用人体气道上皮细胞发现，RSV蛋白NS1（RSV-NS1）会抑制这些细胞中的一个关键生物通路（称为 “JAK/STAT 通路”），阻止关键的 “免疫系统点火器（immune system igniters）”进入细胞核。这种称为STAT1的免疫系统点火器通常由我们自身的天然抗病毒药物——干扰素α（IFNα）激活。 RSV-NS1 的表达能显著增强 IFN-α 介导的 STAT1 磷酸化，但不能增强 pSTAT2；STAT1 和 STAT2 的总蛋白水平均不受 RSV-NS1 的影响。然而，RSV-NS1 的表达能显著降低 ISRE 和 GAS 启动子的活性以及抗病毒 IRG 的表达。进一步的机理研究表明，RSV-NS1 与 STAT1 结合，蛋白建模显示 STAT1 与 RSV-NS1 之间可能存在相互作用位点。在 RSV-NS1 的存在下，STAT1 的细胞核转运减少。此外，STAT1 与核转运适配蛋白 KPNA1 的相互作用也减少了。事实上，减少 STAT1 进入细胞核可能是 RSV 抑制 IFN JAK/STAT 启动子激活和抗病毒基因诱导的原因。图片来自Frontiers in Immunology, 2024, doi:10.3389/fimmu.2024.1395809 Stevenson说，“IFNα通过JAK/STAT通路激活我们细胞中的信号，负责启动数百个抗病毒基因，然后以多种不同的方式攻击这种病毒。因此，当 RSV 阻止干扰素与这些基因沟通时，这种病毒就会对我们的免疫反应踩刹车，这可能导致这种病毒占据上风，并迅速引发非常严重的医疗问题。” “我们的发现是一个令人兴奋的启示，因为它确定了 JAK/STAT 通路是治疗性免疫恢复的主要靶点。这一新知识对药物设计者来说非常有价值，因为他们需要充分了解这种病毒如何躲避我们的免疫系统，然后才能成功地开发出扭转这种局势的疗法。” “我们预测，这类疗法可以在治疗 RSV 方面产生重大影响，甚至可以清除 RSV 感染，这将是儿童和老人急需的解决方案，因为他们非常容易感染这种危险的病毒。”（生物谷Bioon.com）参考资料： Claudia Efstathiou et al. Respiratory syncytial virus NS1 inhibits anti-viral Interferon-α-induced JAK/STAT signaling, by limiting the nuclear translocation of STAT1. Frontiers in Immunology, 2024, doi:10.3389/fimmu.2024.1395809.

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