Molecular cloning and characterization of a novel Rel/NF-kappa B family member displaying structural and functional homology to NF-kappa B p50/p105.
The NF-kappa B transcription factor has been implicated in the inducible expression of many genes, including inflammatory, immune, and acute-phase response genes. NF-kappa B consists of two subunits, 50K and 65K polypeptides. The genes encoding p50 and p65 have sequence similarities with the c-rel proto-oncogene and the Drosophila maternal effect gene dorsal. We describe the cloning and characterization of a novel rel-related gene encoding a 98K product that shares extensive homology with the p105 precursor of the NF-kappa B p50 protein, containing both a Rel homology and SWI6/ankyrin repeat domain. We demonstrate that p98 is proteolytically processed in vivo to generate a 55K polypeptide, which binds to kappa B sites. p55 is capable of forming heterocomplexes with other Rel/NF-kappa B family members, which can bind to kappa B motifs in vitro, and stimulate transcription of reporter genes containing these cis-elements in vivo. The identification of a homolog for NF-kappa B p50/p105, termed p55/p98, gives further support to the idea that NF-kappa B is a collection of structurally related complexes of which contribute to the pleiotropic regulatory processes originally assigned to NF-kappa B.
Mercurio
F
F
Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla 92093-0636.
Didonato
J
J
Rosette
C
C
Karin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics*; D052003:NF-kappa B p52 Subunit; D014411:Neoplastic Stem Cells; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D020569:Proto-Oncogene Proteins c-rel; D012045:Regulatory Sequences, Nucleic Acid; D017385:Sequence Homology; D014158:Transcription, Genetic
D017487:Ankyrins; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D004247:DNA