Related Experiment Video
Updated: Jun 20, 2026

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
Published on: October 6, 2019
IKKalpha negatively regulates IRF-5 function in a MyD88-TRAF6 pathway
Mumtaz Yaseen Balkhi1, Katherine A Fitzgerald, Paula M Pitha
1Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Abstract:
Transcription factors of IRF family, IRF-3, IRF-5 and IRF-7 play a critical role in the innate antiviral response. In infected cells, IRF-3 and IRF-7 are activated by TBK-1 and IKK epsilon mediated phosphorylation, while the kinase, phosphorylating IRF-5 in the MyD88 signalling pathway has not yet been identified. We now show that IKK alpha phosphorylates IRF-5 and induces formation of IRF-5 dimers, which have been indicative of IRF-5 activation. However, IKK alpha induced IRF-5 phosphorylation exerts inhibitory effect on the transcriptional activation of type 1 interferon and promoters of the inflammatory cytokines. Addressing the molecular mechanism of IKK alpha mediated inhibition of IRF-5 activity, we show that phosphorylation of IRF-5 by IKK alpha inhibits K63 ubiquitination that is essential for IRF-5 activity. Furthermore, we have identified interaction of IRF-5 with alkaline phosphatase, which causes its de-phosphorylation. The observation that MyD88 activated IRF-5 induces expression of alkaline phosphatase suggests that IRF-5 is under autoregulating loop. Thus these completely new observations identify IKK alpha kinase and alkaline phosphatase as negative regulators of IRF-5 activity in MyD88 pathway and implicate their role in the control of the inflammatory response by attenuation of IRF-5 activity.
Related Concept Videos
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response
The JAK-STAT Signaling Pathway
NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
TGF - β Signaling Pathway
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...

