Disease relevance of NAB1

• Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies [1].
• Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1 [2].

High impact information on NAB1

• This NGFI-A-binding protein, NAB1, is a 570-aa nuclear protein that bears no obvious sequence homology to known proteins [3].
• Overexpression of Egr-2 and Egr-3 induced endogenous ligand upregulation that was inhibited by overexpression of Egr-specific inhibitor Nab1 [4].
• The human NAB1 genomic locus was mapped to chromosome 2q32.3-33 [5].
• Replacement mutagenesis of residues conserved between these proteins interfered with Nab1 repression, although Nab1 does not function by the same mechanism as Dr1 [5].
• We have isolated and characterized another corepressor, NAB2, which is highly related to NAB1 within two discrete domains [6].

Biological context of NAB1

• Sequencing of the Caenorhabditis elegans genome has identified a gene that bears high homology to both NAB1 and NAB2, suggesting that NAB molecules fulfill an evolutionarily conserved role [6].
• In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo [2].
• Therapeutic applications of the transcriptional corepressor proteins NAB1 and NAB2 in regenerative medicine [7].
• A fusion protein consisting of the DBD of GAL4 and the coding region of human NAB1 repressed transcription from model promoters with engineered upstream GAL4 binding sites [8].

Anatomical context of NAB1

• Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils [2].
• We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells [2].
• NAB1 is expressed ubiquitously in human cell lines as shown by RNase protection mapping [8].

Physical interactions of NAB1

• Therefore, we hypothesized that mutations in the EGR2-interacting domains of NAB1 and NAB2 might be associated with the pathogenesis of inherited peripheral neuropathies in currently unexplained cases [1].
• Thus, the biological function of the inhibitory domain of Egr-1 is solely to provide a docking site for NAB1 via protein-protein interaction [8].

Other interactions of NAB1

• Overexpression studies revealed that NAB1 is able to completely block transcription mediated by Egr-1 [8].

References