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Updated: Jun 26, 2026

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity
S Haskill1, A A Beg, S M Tompkins
1Lineberger Comprehensive Cancer Center, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599.
Abstract:
We have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes. One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdc10/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-kappa B/KBF1 p50. The C-terminus has a putative protein kinase C phosphorylation site. In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p50/p65 NF-kappa B complex but not that of the p50/p50 KBF1 factor or of other DNA-binding proteins. The MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation.
Insights
Researchers identified a novel protein, MAD-3, that regulates NF-kappa B activity in human monocytes. This discovery sheds light on monocyte activation pathways and inflammatory responses.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Monocyte adherence triggers rapid gene expression changes.
- Nuclear factor kappa B (NF-kappa B) is a key transcription factor involved in immune responses.
Purpose of the Study:
- To identify and characterize novel genes rapidly induced upon human monocyte adherence.
- To investigate the function of the identified MAD-3 protein in regulating NF-kappa B activity.
Main Methods:
- Cloning of cDNAs representing induced mRNAs.
- Protein sequence analysis and motif identification.
- In vitro translation and DNA-binding assays.
Main Results:
- A novel transcript, MAD-3, was cloned and found to encode a protein with ankyrin repeats.
- MAD-3 protein specifically inhibits the DNA-binding activity of the NF-kappa B p50/p65 complex.
- MAD-3 exhibits structural similarity to I kappa B proteins.
Conclusions:
- MAD-3 is an I kappa B-like protein involved in regulating NF-kappa B-dependent transcription.
- MAD-3 plays a role in adhesion-dependent pathways of monocyte activation.
- This finding contributes to understanding transcriptional regulation in immune cells.
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