Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation.

Published

Journal Article

The transcription factor NF-kappaB regulates genes involved in innate and adaptive immune response, inflammation, apoptosis, and oncogenesis. Proinflammatory cytokines induce the activation of NF-kappaB in both transient and persistent phases. We investigated the mechanism for this biphasic NF-kappaB activation. Our results show that MEKK3 is essential in the regulation of rapid activation of NF-kappaB, whereas MEKK2 is important in controlling the delayed activation of NF-kappaB in response to stimulation with the cytokines TNF-alpha and IL-1alpha. MEKK3 is involved in the formation of the IkappaBalpha:NF-kappaB/IKK complex, whereas MEKK2 participates in assembling the IkappaBbeta:NF-kappaB/IKK complex; these two distinct complexes regulate the proinflammatory cytokine-induced biphasic NF-kappaB activation. Thus, our study reveals a novel mechanism in which different MAP3K and IkappaB isoforms are involved in specific complex formation with IKK and NF-kappaB for regulating the biphasic NF-kappaB activation. These findings provide further insight into the regulation of cytokine-induced specific and temporal gene expression.

Full Text

Duke Authors

Cited Authors

  • Schmidt, C; Peng, B; Li, Z; Sclabas, GM; Fujioka, S; Niu, J; Schmidt-Supprian, M; Evans, DB; Abbruzzese, JL; Chiao, PJ

Published Date

  • November 2003

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 1287 - 1300

PubMed ID

  • 14636585

Pubmed Central ID

  • 14636585

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(03)00390-3

Language

  • eng