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Transcriptional activation by NF-kappaB requires multiple coactivators
K A Sheppard1, D W Rose, Z K Haque
1Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Molecular and Cellular Biology
|August 24, 1999
Summary
Nuclear factor-kappaB (NF-kappaB) recruits coactivators similar to nuclear receptors. This process requires specific proteins and histone acetyltransferase activity for gene regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Epigenetics
Background:
- Nuclear factor-kappaB (NF-kappaB) is a key transcription factor regulating inflammation and cell survival.
- Understanding NF-kappaB's regulatory mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the coactivator complex recruited by NF-kappaB.
- To compare NF-kappaB coactivator recruitment with that of nuclear receptors.
- To elucidate the differential roles of NF-kappaB subunits in gene expression.
Main Methods:
- Nuclear antibody microinjection to inactivate coactivator proteins.
- Assessing NF-kappaB-dependent transactivation.
- Analyzing the role of specific protein motifs (LXXLL) and histone acetyltransferase (HAT) activity.
Main Results:
- NF-kappaB recruits a coactivator complex resembling that of nuclear receptors.
- Inactivation of CBP, p160 family members, or p/CAF inhibits NF-kappaB transactivation.
- NF-kappaB-dependent gene expression requires LXXLL motifs and p/CAF's HAT activity, but not CBP's.
- The p50 homodimer does not recruit coactivators, while the p50-p65 heterodimer does.
Conclusions:
- NF-kappaB utilizes a coactivator complex with similarities to nuclear receptors.
- Specific coactivator components and their enzymatic activities are essential for NF-kappaB function.
- Differential recruitment of coactivators by NF-kappaB subunits (p50 vs. p50-p65) explains their distinct effects on gene expression.