Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity

Abstract

Fos and Jun family proteins regulate the expression of a myriad of genes in a variety of tissues and cell types. This functional versatility emerges from their interactions with related bZIP proteins and with structurally unrelated transcription factors. These interactions at composite regulatory elements produce nucleoprotein complexes with high sequence-speci®city and regulatory selectivity. Several general principles including binding cooperativity and conformational adaptability have emerged from studies of regulatory complexes containing Fos-Jun family proteins. The structural properties of Fos-Jun family proteins including opposite orientations of heterodimer binding and the ability to bend DNA can contribute to the assembly and functions of such complexes. The cooperative recruitment of transcription factors, coactivators and chromatin remodeling factors to promoter and enhancer regions generates multiprotein transcription regulatory complexes with cell-and stimulus-speci®c transcriptional activities. The genespeci®c architecture of these complexes can mediate the selective control of transcriptional activity. Oncogene (2001) 20, 2438 ± 2452.

Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs

“…We next investigated whether all three AP-1 transcription factors were able to repress paox expression by directly acting on its promoter. For this purpose, we cloned a portion of the paox promoter ( À 3045 to À 997) predicted by TESS (Transcription Element Search System online software) to contain two potential AP-1-binding sites (indicated as P1 and P2 in Figure 2d 25,27 and expectedly, AP-1 monomers that were tethered to force specific pairing of c-Jun/FosB and JunB/FosB 26 suppressed paox or activated collagenase to a higher level relative to c-Jun, JunB and FosB alone ( Figure 2d, lower panels). In order to locate the binding sites for AP-1 on the paox promoter, the two predicted repressor sites (P1 and P2) were mutated.…”

“…24 Although AP-1 members can activate a set of common target genes, different AP-1 dimer compositions produce different biological outcomes, suggesting that they can also selectively regulate distinct sets of genes. 25,26 In addition, some biological effects of AP-1 members are the result of their ability to repress gene expression, such as inhibition of p53 by c-Jun. 27 In this respect, we have investigated the mechanism of DNp73 regulation through the Az pathway with reference to the specificity of AP-1 members in regulating this process.…”

Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1

“…AP-1 is a central component of many signal transduction pathways in a variety of cell types, and is critical for mitogenesis, apoptosis and carcinogenesis in a cell type-specific manner (Ludes-Meyers et al, 2001;Eferl and Wagner, 2003;Matthews et al, 2007). AP-1 comprises a variety of dimeric bZIP proteins that belong to the Jun, Fos, Maf and ATF subfamilies (Chinenov and Kerppola, 2001). Among the Jun proteins, c-Jun is the most potent transcriptional activator, and the c-Fos-c-Jun heterodimer positively regulates cell proliferation and transformation (Maki et al, 1987;Angel and Karin, 1991;Ryseck and Bravo, 1991).…”

A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells

“…These proteins form dimers that recognize the TPAresponse element and other consensus motifs (for example, CRE, ARE, NFkB, E2F) in the promoter/ enhancer regions of genes that regulate cell proliferation, survival, differentiation and migration (Karin et al, 1997;Chinenov and Kerppola, 2001).…”