A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site.

Abstract

NF-KB denotes a transcription factor which has been implicated in the induced expression of many genes and viruses (for reviews see references 2 and 27). NF-KB is presumed to exert its effect through binding to cis-acting, so-called KB elements present in the respective promotersenhancers. The original KB site was defined as an essential functional component of the intronic immunoglobulin K light-chain enhancer, and its decameric sequence is GGGAC TTTCC (the KB consensus sequence reads GGGRNNY YCC). Included among the NF-KB-responsive genes are many involved in immune responses and/or acute-phase reactions, such as the cytokines interleukin-2, interleukin-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha, as well as the interleukin-2 receptor a, the immunoglobulin K light chain, and angiotensinogen. In has been recognized to exist as a heterodimer of a p50 and a p65 subunit (47). p50 can form homodimers, but it is the heterodimer that is thought to be the primary transactivating complex owing to potentially transactivating sequences present in p65 (34,38).The genes encoding NF-KB have recently been cloned. p50 is part of a larger precursor protein of 105 kDa. We have cloned this gene, originally designated 243, as a mitogeninduced cDNA selected from a collection of such clones which harbor immediate-early response genes (6), and others have cloned this gene by using nucleic acid probes based on partial peptide sequences of purified p50 protein (13,24,31). The 105-kDa precursor protein consists of two main domains, an amino-terminal region of about 300 amino acids related to the amino-terminal part of the c-Rel protein (7) and a carboxy-terminal portion containing several so-called cell cycle or ankyrin repeat structures. The carboxy-terminal domain inhibits binding of the precursor protein to DNA. Upon removal of the repeat domain by proteolytic cleavage, the amino-terminal region corresponding to the p50 protein and containing all sequences related to c-Rel specifically binds KB DNA elements (37). The p65 gene also encodes a 38). c-Rel, p50, and p65 share extensive homology in their amino-terminal regions, the so-called Rel homology domain, but differ elsewhere. c-Rel and p65 do not contain the cell cycle (ankyrin) repeats. The finding that p50 and p65 are related to c-Rel and bind KB sites has led to the recent discovery that the c-rel proto-oncogene and the v-rel oncogene products are also capable of binding KB DNA. However, only c-Rel transactivates, whereas v-Rel inhibits KB-dependent transcription (5,19,23,36). In addition, a rel-related drosophila gene product, Dorsal, which is the essential morphogenic determinant for ventraldorsal polarity, binds to sites closely resembling KB sites and activates gene expression (20,45). These observations suggest a family of NF-KB-like complexes which together are responsible for the pleiotropic cellular effects originally ascribed to just one transcription factor complex. 685on May 7, 2018 by guest

Additive effect between NF-κB subunits and p53 protein for transcriptional activation of human p53 promoter

“…The PMT2T expression vector encoding the RelA NF-kB subunit was previously described (Bours et al, 1992). The expression vector for wild-type p53 (pC53-SN3) was provided by Dr U Gullberg (University of Lund, Sweden).…”

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

“…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).…”

Nuclear Factor-κB2 Represses Sp1-Mediated Transcription at the CD99 Promoter

“…Despite having lowaffinity BCRs, HL cells can be resistant to signal-induced apoptosis due to constitutively active NF-κB survival signals (Bours et al, 1992).…”

“…In lymphoid cells, where rearrangement and somatic mutations in the antigen receptor are the most lineage-specific events, analysis of the immunoglobulin heavy chain locus in HLRSCs clearly implicated germinal center B cells as the HLRSC origin (Braeuninger et al, 1997;Ohno et al, 1997). The neoplastic Reed-Sternberg cells in Hodgkin's lymphoma (HL) are characterized by constitutively activated NF-κB (Bours et al, 1992), due to over-expression of potent NF-κB-activating TNF receptor family proteins (CD40, CD30, or EBV LMP1) (Cabannes et al, 1999;Sylla et al, 1998) or mutation in the inhibitor of the NF-κBα gene (IκBα) Krappmann et al, 1999). However, the pathogenesis of HL remains unclear.…”

“…The NF-κB complex is constitutively activated in HLRSCs (Bours et al, 1992). The mechanisms underlying high NF-κB activity in HLRSCs include mutation of IκB, modification of NF-κBs, constitutive IKKβ expression, and EBV infection (Cabannes et al, 1999;Emmerich et al, 1999;Jundt et al, 1999;Krappmann et al, 1999;Wood et al, 1998).…”