• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The role of phosphorylation of p65 subunit on transcriptional activity of NF-κB

Research Project

Project/Area Number 16390536
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionKyushu Dental College (2005)
Fukuoka Dental College (2004)

Principal Investigator

JIMI Eijiro  Kyushu Dental College, School of Dentistry, Professor, 歯学部, 教授 (40276598)

Co-Investigator(Kenkyū-buntansha) OKABE Koji  Fukuoka Dental College School of Dentistry, Professor, 歯学部, 教授 (80224046)
OKAMOTO Fujio  Fukuoka Dental College School of Dentistry, Lecturer, 歯学部, 講師 (60153938)
KAJIYA Hiroshi  Fukuoka Dental College School of Dentistry, Assistant Professor, 歯学部, 助手 (80177378)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥9,800,000 (Direct Cost: ¥9,800,000)
KeywordsTranscription factor / NF-κB / Phosphorylation
Research Abstract

The transcription factor NF-κB, which is critical for inducible expression of many genes involevdinimmunity and inflammation, exists in the cytosol of resting cells bound to inhibitory IκB proteins. Stimulation with specific inducers, such as TNFα or LPS activates an IκB kinase (IKK) complex that phosphorylates IκB, triggering its degradation by the proteasome and allowing free NF-κB to translocate to the nucleus and activate gene expression. Recent evidence supports the role for phosphorylation of NF-κB p65 subunit in determining the transcriptional capacity of NF-κB. Several studies provide the basis for systemic examination of the mechanisms through which distinct kinases influence the transcriptional activity of NF-κB. We have shown that the catalytic subunit of PKA phosphorylatesp65 subunit at Ser 276 positively regulates transcriptional activity of NF-κB in vitro. To address the physiological role of p65 phosphorylation by PKA, we generated knock-in mice, which replace at Ser 276 to Ala (S276A). S276A knock-in mice died around ED18.5 due to a failure to separate emerging lymphatic vessels from blood vessels. Furthermore, some S276A embryos showed eye defect.
It has been accumulating that IKKβ directly phosphorylates p65 subunit at Ser 534 to induce transcriptional activity of NF-κB. To address the importance of Ser 534, we have also been generating new knock-in mice, which replace at Ser 534 to Ala (S534A). We have gotten 3 positive ES clones, which have homologous recombination in wild-type allele to knock-in allele.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi