# Understanding the importance of IkB-b as a selective co-activator of NF-kB signaling

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $400,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The transcription factors of the NF-kB family are central regulators of a wide variety of biological processes.
This includes events as fundamental as embryonic development and cellular survival as well as the intricate
responses of the innate and adaptive immune system. What has remained elusive are the mechanisms that
allow this limited set of five proteins to orchestrate the radically different transcriptional programs which are
required for these disparate cellular functions. Understanding the details of NF-kB-dependent transcription,
however, is of paramount importance for efforts to achieve targeted therapeutic intervention in cases of
pathological NF-kB activation, such as sepsis, rheumatoid arthritis and cancer.
One of the factors that fine-tune NF-kB activation is the inhibitor of NF-kB, isoform b (IkB-b), which has been
shown to serve an intriguing dual role as a conventional inhibitor, and atypical co-activator, of NF-kB-
dependent transcription. In unstimulated cells, IkB-b sequesters NF-kB dimers in the cytoplasm and thus
prevents transcriptional activation, whereas upon stimulation a nuclear form of IkB-b enhances transcription of
a subset of NF-kB-dependent genes. Consequently, IkB-b-deficient macrophages produce starkly reduced
levels of the cytokine TNF-a following exposure to an activating stimulus, whereas levels of the cytokine IL-6
are largely unaffected.
The goal of this project is to comprehensively understand the role of IkB-b as a selective co-activator of NF-kB
activation. This will be accomplished by rigorously characterizing the mechanism that underlies IkB-b function
on a biochemical and molecular level. Furthermore, the full extent of IkB-b co-activator function and its effect
on global transcription will be probed using cutting-edge genomics techniques, including RNA-seq and ChIP-
seq. These data sets will then be integrated to create a holistic model of IkB-b function. Finally, the true
physiological relevance of IkB-b will be determined in vivo with mouse models of acute and chronic
inflammation, as well as bacterial infection.

## Key facts

- **NIH application ID:** 10153691
- **Project number:** 5R01AI139217-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Sankar Ghosh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153691

## Citation

> US National Institutes of Health, RePORTER application 10153691, Understanding the importance of IkB-b as a selective co-activator of NF-kB signaling (5R01AI139217-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153691. Licensed CC0.

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