Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the interleukin-1β-stimulated C/EBP signaling pathway.

ABSTRACT: Interleukin-1β (IL-1β) is a key proinflammatory cytokine that initiates several signaling cascades, including those involving CCAAT/enhancer binding proteins (C/EBPs). The mechanism by which IL-1β propagates a signal that activates C/EBP has remained elusive. Nemo-like kinase (NLK) is a mitogen-activated protein kinase (MAPK)-like kinase associated with many pathways and phenotypes that are not yet well understood. Using a luciferase reporter screen, we found that IL-1β-induced C/EBP activation was positively regulated by NLK. Overexpression of NLK activated C/EBP and potentiated IL-1β-triggered C/EBP activation, whereas knockdown or knockout of NLK had the opposite effect. NLK interacted with activating transcription factor 5 (ATF5) and inhibited the proteasome-dependent degradation of AT

SUBMITTER: Zhang ZY 

PROVIDER: S-EPMC4323494 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature