Molecular Cloning and Characterization of NAKBP, which bind to a novel IKK-Kinase, NAK

• Project/Area Number: 14570490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: TAKASHI Joh (2003) Nagoya City University, Graduate School of Medical Sciences, Associate Proffesor., 大学院・医学研究科, 助教授 (30231369); 妹尾 恭司 (2002) 名古屋市立大学, 大学院・医学研究科, 助手 (30295589)
• Co-Investigator(Kenkyū-buntansha): NAKANISHI Makoto Nagoya City University, Graduate School of Medical Sciences, Proffesor, 大学院・医学研究科, 教授 (40217774) ; 城 卓志 名古屋市立大学, 大学院・医学研究科, 助教授 (30231369)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: NAP1 / NF-κB / TNF-α / NAK / Gastritis / Inflammatory Bowel Disease / Transcription Factor / Molecular Mechanism / 炎症性腸疾息 / IKK / NAKBP

Research Abstract

The IκB kinase (IKK)-related kinase NAK (also known as TBK or T2K) contributes to the activation of NF-κB-dependent gene expression. Here we identify NAP1 (for NAK-associated protein 1), a protein that interacts with NAK and its relative IKKε(also known as IKKi). NAP1 activates NAK and facilitates its oligomerization. Interestingly, the NAK-NAP1 complex itself effectively phosphorylated serine 536 of the p65/RelA subunit of NF-κB, and this activity was stimulated by tumor necrosis factor alpha (TNF-α).
Overexpression of NAP1 specifically enhanced cytokine induction of an NF-κB-dependent reporter gene expression and sensitized cells to TNF-α-induced apoptosis. These results define NAP1 as an activator of IKKK-related kinases and suggest that the NAK-NAP1 complex may protect cells from TNF-α-induced apoptosis by promoting NF-κB activation.

Research Products

• [Publications] Fumitaka Fujita, Takashi Joh, Makoto Nakanishi ら: "Identification of NAP1, a Regulatory Subunit of IκB Kinase-Related Kinases That Potentiates NF-κB Signaling"Molucular and Cellular Biology. 23-21. 7780-7793 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 藤田史岳, 城卓志, 中西真, 伊藤誠ら: "G.I.Research, vol.11 no.4"株式会社先端医学社. 360-361 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fumitaka Fujita, Takashi Joh, Mokoto Nakanishi: "Identification of NAP1, a Regulatory Subunit of IκB Kinase-Related Kinases That Potentiates NF-κB Signaling"Molucular and Cellular Biology. 23-21. 7780-7793 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fumitaka Fujita, Takashi Joh, Makoto Nakanishi: "Identification of NAP1, a Regulatory Subunit of IκB Kinase-Related Kinases That Potentiates NF-κB Signaling"Molucular and Cellular Biology. 23・21. 7780-7793 (2003)