title: LATS2 inhibits the activity of NF-κ B signaling by disrupting the interaction between TAK1 and IKKβ.
abstract: NF-κB signaling plays very important role in the tumorigenesis of nonsmall cell lung cancer (NSCLC). However, the molecular mechanisms for the dysregulation of NF-κB signaling in NSCLC have not been fully understood. In the previous reports, we have showed that large tumor suppressor gene 2 (LATS2) inhibited NF-κB signaling in NSCLC cells, whereas the details for the mechanism remain unknown. Here, we reported that LATS2 is a suppressor of tumor necrosis factor (TNF-α)-induced NF-κB signaling by inhibiting the interaction between TAK1 and IKKβ. Overexpression of LATS2 largely blocked TNF-α-induced NF-κB activation and IκBα degradation, whereas knockdown of LATS2 showed the opposing results. Mechanistically, we identified that LATS2 interacted with IKKβ and blocked the interaction between IKKβ and TAK1. Our results indicate that LATS2 functions as a pivotal negative regulator in TNF-α-induced activation of NF-κB via disrupting the interaction of TAK1 with IKKβ.
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. zhouweizheng1118@163.com.
authors.forename: Weizheng
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China. fangwentao0808@163.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Fang
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D051550:I-kappa B Kinase; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D000099151:MAP Kinase Kinase Kinase 7; C439524:TNF protein, human; C406449:LATS2 protein, human; C496560:IKBKB protein, human
keywords: IKK complex; LATS2; NF-κB signaling; Nonsmall cell lung cancer; TAK1; TNF-α