Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits.

Abstract

The promoter of the human major histocompatibility complex class II-associated invariant-chain gene (Ii) contains two NF-KB/Rel binding sites located at -109 to -118 (Ii KB-1) and -163 to -172 (Ii KB-2) from the transcription start site. We report here that the differential function of each of these NF-KB/Rel sites in several distinct cell types depends on cell-specific binding of NF-KB/Rel transcription factors. Ii KB-1 is a positive regulatory element in B-cell lines and in the li-expressing T-cell line, H9, but acts as a negative regulatory element in myelomonocytic and glial cell lines. In vivo protein-DNA contacts are detectable at Ii KB-1 in cell lines in which this site is functional as either a positive or negative regulator. Electrophoretic mobility supershift assays determine that members of the NF-KB/Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50, p52, p65, and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation. Ii KB-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells, myelomonocytic, and glial cell lines. In vivo occupancy of this site is observed only in the H9 T-cell line. Again

Recombinant MPT83 Derived fromMycobacterium tuberculosisInduces Cytokine Production and Upregulates the Function of Mouse Macrophages through TLR2

“…The inhibition of NF-kB activation in dendritic cells decreases the expression of MHC-II and costimulatory molecules and, thereby, decreases the priming of T cells (70). NF-kB binding sites within the MHC-II invariant chain promoter are downregulated by the NF-kB subunit, p50, in promonocytic U937 cells (71). Recent evidence suggested that NF-kB may also play a role in resolving inflammation, because a shift in NF-kB subunits from p50-p65 to p50 homodimers is associated with the resolution of inflammation (69,72).…”

A κB-related Binding Site Is an Integral Part of the mts1 Gene Composite Enhancer Element Located in the First Intron of the Gene

“…However, to our knowledge this sequence has never been described as a functional B site before. The functional B sites most similar to the Sb sequence have been found in the ␥-interferon intronic enhancer (GAATTTTCC) (32) and in the promoter of the major histocompatibility complex class II associated invariant chain gene (GGGTATTTCC) (33).…”

Activation of p65 NF-κB protein by p210BCR – ABL in a myeloid cell line (P210BCR – ABL activates p65 NF-κB)

“…The dierence with our results can be attributed to the fundamental dierences between BCR ± ABL and v-abl regarding to their structure, their cellular localization, their transforming potential in ®broblasts, their interaction with signaling proteins and the induced disease in vivo (Cook, 1982;Daley et al, 1987Daley et al, , 1990McWhirter and Witte, 1991;McWhirter et al, 1993;Reuther et al, 1994;Varticovski et al, 1991). In addition, inhibition of NF-kB activity by v-abl can only be restricted to pre-B cells and the v-abl tyrosine kinase since NF-kB activity is dierentially regulated depending on the cell type and the involved stimuli (Brown et al, 1994;Lernbecher et al, 1993;Shu et al, 1993).…”

“…NFkB family contains several members which bind DNA as homodimers or heterodimers (p100-p50 (NF-kB1), p105-p52 (NF-kB2), c-Rel, p65 (RelA) and RelB). Regulation of REL/NF-kB family members occur at dierent levels and their activity is strictly controlled to mediate speci®c gene and cell responses (Brown et al, 1994;Dobzranski et al, 1994;Kunsch et al, 1992;Lernbecher et al, 1993;Liou and Baltimore, 1993;Naumann and Scheidereit, 1994;Perkins et al, 1992;Schmitz and Baeuerle, 1995). REL/NF-kB proteins and their regulators IkB proteins have been associated with a number of viral and non viral malignancies (Gilmore et al, 1996).…”