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

Abstract

The transcription factor NF-kappa B 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). Both the 50K and 65K subunits have similarity with the rel oncogene and the Drosophila maternal effect gene dorsal. 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-kappa B. It is more similar to p105 NF-kappa B than other family members and defines a new subset of rel-related genes. It is synthesized as approximately 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 kappa B DNA-binding activity and can form heterodimers with other rel proteins. In contrast to the approximately 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/p100 NF-kappa B could therefore be important in the regulation of HIV and other kappa B-containing genes.

Regulation of NF-κB activity by IκB-related proteins in adenocarcinoma cells

“…They both contain ankyrin repeats and sequester NF-kB complexes in the cytoplasm (Bours et al, 1990Kieran et al, 1990;Neri et al, 1991;Schmid et al, 1991;Mercurio et al, 1992Mercurio et al, , 1993Rice et al, 1992). These precursors are cleaved in order to liberate nuclear-prone p50 or p52 proteins (Fan and Maniatis, 1991;Mercurio et al, 1993).…”

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

“…The classic, inducible NF-kB transcriptional activator is composed of the heterodimer of p50 NF-kB-1 and p65 RelA molecules Baltimore, 1988, 1989). Homodimers of p50 NF-kB-1 and p52 NF-kB-2, which lack a discrete transcriptional activation domain, generally exhibit transcriptional repression properties, presumably through binding to kB motifs in the promoters of target genes and inhibiting binding of the strongly activating NF-kB dimers (Franzoso et al, 1992;Fujita et al, 1992;Schmid et al, 1991). Interestingly, a small subset of NFkB target genes can be directly transcriptionally activated by these homodimers, apparently as a result of conformational changes in the proteins induced upon binding to speci®c subsets of kB DNA motifs (Fujita et al, 1992;Pan and McEver, 1995).…”

An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

“…Both gene products require proteolytic processing to generate the -50-kDa amino terminus DNA-binding forms, NF-KB1(pSO) and NF-KB2(p52) (8,19,43). A shorter alternatively spliced transcript of NF-KB2 has also been identified; it gives rise to a 49-kDa protein, NF-KB2(p49), identical to the amino-terminal Rel domain of NF-KB2(plOO), and thus does not require processing to generate the DNA-binding form (62) but otherwise has activities identical to those of NF-KB2(p52) (54). The DNA-binding and dimerization functions of NF-KB subunits have been shown to be encoded by the amino-and carboxyterminal regions, respectively, of the Rel-conserved domain (11,13,35,42,73).…”

“…The ReIA(p65) and RelB subunits are most highly homologous to c-Rel (49,58,59,61) and contain transactivation domains in their carboxy termini (12,27,31,49,55,60,61,63). Two related cDNAs encoding the larger precursor proteins of the 50-kDa DNAbinding subunits of NF-KB, NF-KB1(p105) (10,22,34,44) and NF-KB2(plOO) (9,47,62), have been isolated. Both gene products require proteolytic processing to generate the -50-kDa amino terminus DNA-binding forms, NF-KB1(pSO) and NF-KB2(p52) (8,19,43).…”

“…The release of the active NF-KB-binding protein is thought to be controlled by the phosphorylation of different IKB gene products (3,7,21,26,32,48,65,78). Other potential regulatory steps include the processing of the high-molecular-weight precursor of the -50-kDa DNA-binding subunit (19,43,56), the differential regulation of NF-KB mRNAs (1), or the formation of specific heteromeric complexes by different family members (25,36,54,62,66).…”