Related Experiment Video
Updated: Dec 12, 2025

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
IκB kinase-ε-mediated phosphorylation triggers IRF-1 degradation in breast cancer cells
Anna Lisa Remoli1, Marco Sgarbanti1, Edvige Perrotti1
1Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
Abstract:
Interferon Regulatory Factors (IRFs) are key regulators of immunity, cell survival and apoptosis. IRF transcriptional activity and subcellular localization are tightly regulated by posttranscriptional modifications including phosphorylation. The IκB kinase family member IKK-ε is essential in regulating antiviral innate immunity mediated by IRFs but is now also recognized as an oncoprotein amplified and overexpressed in breast cancer cell lines and patient-derived tumors. In the present study, we report that the tumor suppressor IRF-1 is a specific target of IKK-ε in breast cancer cells. IKK-ε-mediated phosphorylation of IRF-1 dramatically decreases IRF-1 protein stability, accelerating IRF-1 degradation and quenching IRF-1 transcriptional activity. Chemical inhibition of IKK-ε activity, fully restores IRF-1 levels and function and positively correlates with inhibition of cell growth and proliferation of breast cancer cells. By using a breast cancer cell line stably expressing a dominant negative version of IRF-1 we were able to demonstrate that IKK-ε preferentially exerts its oncogenic potential in breast cancer through the regulation of IRF-1 and point to the IKK-ε-mediated phosphorylation of IRF-1 as a therapeutic target to overcome IKK-ε-mediated tumorigenesis.
Related Concept Videos
Regulation of the Unfolded Protein Response
PI3K/mTOR/AKT 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...
MAPK Signaling Cascades
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

