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 dorsal3–6. 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.