Cloning of an NF-κB subunit which stimulates HIV transcription in synergy with p65

Abstract

THE transcription factor NF-κB is a protein complex which comprises a DNA-binding subunit and an associated transactivation protein (of relative molecular masses 50,000 (50K) and 65K, respectively)^1,2. Both the 50K and 65K subunits have similarity with the rel oncogene and the Drosophila maternal effect gene dorsal^3–6. The 50K DNA-binding subunit was previously thought to be a unique protein, derived from the 105K gene product (p105). We now report the isolation of a complementary DNA that encodes an alternative DNA-binding subunit of NF-κB. It is more similar to p105 NF-κB than other family members and defines a new subset of rel-related genes. It is synthesized as a ∼100K protein (p100) that is expressed in different cell types, contains cell cycle motifs and, like p105, must be processed to generate a 50K form. A 49K product (p49) can be generated independently from an alternatively spliced transcript; it has specific κB DNA-binding activity and can form heterodimers with other rel proteins. In contrast to the ∼50K protein derived from p105, p49 acts in synergy with p65 to stimulate the human immunodeficiency virus (HIV) enhancer in transiently transfected Jurkat cells. p49/plOO NF-κB could therefore be important in the regulation of HIV and other κB-containing genes.