Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 35, Issue 5, Pages 778-788Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01228-14
Keywords
-
Categories
Funding
- National Basic Research Program of China [2011CB944404]
- National Natural Science Foundation of China [81270306]
- National Science and Technology Support Project [2012BAI39B02, 2012BAI39B03, 2014BAI02B01]
- Trans-Century Training Programme Foundation for the Talents [NCET-10-0655]
- Fundamental Research Funds for the Central Universities [204275771]
Ask authors/readers for more resources
Interleukin-1 beta (IL-1 beta) is a key proinflammatory cytokine that initiates several signaling cascades, including those involving CCAAT/enhancer binding proteins (C/EBPs). The mechanism by which IL-1 beta 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-1 beta-induced C/EBP activation was positively regulated by NLK. Overexpression of NLK activated C/EBP and potentiated IL-1 beta-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 ATF5 in a kinase-independent manner. Consistently, NLK deficiency resulted in decreased levels of ATF5. NLK cooperated with ATF5 to activate C/EBP, whereas NLK could not activate C/EBP upon knockdown of ATF5. Moreover, TAK1, a downstream effector of IL-1 beta that acts upstream of NLK, mimicked the ability of NLK to stabilize ATF5 and activate C/EBP. Thus, our findings reveal the TAK1-NLK pathway as a novel regulator of basal or IL-1 beta-triggered C/EBP activation though stabilization of ATF5.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available