Nemo样激酶在机体发育和疾病中作用机制研究进展  

Research progress on the role of NLK in development and disease

作　　者：王曼伊 王光丽 赵芹[1] 黄冰怡 冯乔[1] WANG Manyi;WANG Guangli;ZHAO Qin;HUANG Bingyi;FENG Qiao(Affiliated Hospital of Guilin Medical University,Guilin 541001,China)

机构地区：[1]桂林医学院附属医院遗传与精准医学实验室,桂林541001

出　　处：《华夏医学》2025年第1期16-21,共6页Acta Medicinae Sinica

基　　金：广西壮族自治区卫健委自筹经费科研项目(Z20211402)。

摘　　要：Nemo样激酶(NLK)是一种进化保守的非典型脯氨酸定向的丝裂原活化蛋白激酶(MAPK),一直被认为是Wnt/β-catenin信号通路的负调节因子,通过不同途径调节Wnt信号传导发挥生理学作用。除了Wnt信号外,NLK通过TAB2作为支架蛋白使NLK与转化生长因子-β活化激酶1(TAK1)相互作用,直接促使组蛋白去乙酰化酶1(HDAC1)磷酸化,参与机体如肺、心脏和骨骼等多器官发育。此外,NLK能够通过其他重要细胞信号传导途径,如Notch、NF-κB、STAT等通路影响骨骼正常发育。NLK还可以通过上述相关途径调节免疫细胞,包括CD8^(+)SP胸腺细胞、Treg细胞增强机体的抗病毒能力。值得关注的是,NLK通过不同信号途径参与喉癌、膀胱癌、前列腺癌、乳腺癌和黑色素瘤等不同肿瘤细胞的发生和发展,下调NLK表达可抑制或逆转肿瘤细胞的增殖、迁移和侵袭,表明NLK可能作为肿瘤细胞发生、发展和诊断的潜在靶点。此外,NLK还参与调节神经退行性疾病的发病过程,例如亨廷顿病和脊髓小脑共济失调。本文就NLK在机体发育和相关疾病发生和发展的机制进行综述。Nemo-like kinase(NLK)is an evolutionarily conserved,atypical proline-directed mitogen-activated protein kinase(MAPK),which has been identified as a negative regulator of the Wnt/β-catenin signaling pathway.NLK plays a critical role in regulating Wnt signaling through various mechanisms.In addition to its role in Wnt signaling,NLK interacts with transforming growth factor-β-activated kinase 1(TAK1)via the scaffolding protein TAB2,promoting the phosphorylation of histone deacetylase 1(HDAC1)and contributing to the development of multiple organs,such as the lung,heart,and bone.Furthermore,NLK influences normal bone development through other important cellular signaling pathways,including Notch,NF-κB,and STAT.NLK also modulates immune cells,including CD8^(+)single-positive(SP)thymocytes and Treg cells,to enhance the body's antiviral responses.Notably,NLK is involved in the initiation and progression of various cancers,including laryngeal,bladder,prostate,breast cancer,and melanoma,through different signaling pathways.Downregulation of NLK expression can inhibit or reverse tumor cell proliferation,migration,and invasion,suggesting that NLK may serve as a potential target for tumorigenesis,development,and diagnosis.Additionally,NLK is implicated in the pathogenesis of neurodegenerative diseases,such as Huntington's disease and spinocerebellar ataxia.This article reviews the mechanisms through which NLK regulates body development and contributes to the occurrence and progression of various diseases.

关 键 词：Nemo样激酶 WNT信号 发育 肿瘤 免疫 

分 类 号：R730.2[医药卫生—肿瘤]