The Complete Exon-Intron Structure of the 156-kb Human Gene NFKB1, Which Encodes the p105 and p50 Proteins of Transcription Factors NF-κB and IκB-γ: Implications for NF-κB-Mediated Signal Transduction

Abstract

The NFKB1 gene encodes three proteins of the NF-κB/Rel and IκB families: p105, p50, and (in mouse) IκB-γ. We determined the complete genomic structure of human NFKB1. NFKB1 spans 156 kb and has 24 exons with introns varying between 40,000 and 323 bp in length. Although NFKB2 , which encodes p100 and p52, also has 24 exons and has a comparable exon-intron structure, it is 20 times shorter (8 kb; Fracchiola et al. (1993) Oncogene 8, 2839-2845) than NFKB1. We propose that the long size of NFKB1 is important for transient activation of NF-κB complexes containing p50. IκB-γ corresponds to the carboxyl-terminal half of p105. DNA sequence analysis showed that the 3′-end of human intron 11 and the 5′-end of exon 12 of NFKB1 are colinear with the 5′-untranslated region of mouse IκB-γ cDNA. IκB-γ is thus likely to be generated by transcription starting within intron 11 and not by alternative splicing of the mouse mRNA encoding p105 and p50.