Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins.

Abstract

Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine the contribution of individual leucine residues to the formation of a stable Fos-Jun protein complex and the binding of this complex to the AP-1 site. Mutation of a single leucine in either Fos or Jun had no effect on protein complex formation. Furthermore, mutations of two consecutive leucines in Jun did not interfere with heterodimer formation; however, in the case of Fos, two consecutive mutations resulted in an inability to form a heterodimer. Although mutagenesis of the first leucine of the heptad repeat had no effect on protein complex formation, this mutation in either Fos or Jun drastically reduced the affinity of the complex for DNA. Thus, both Fos and Jun contribute directly to the DNA-binding potential of the heterodimer.

Small Interference RNA-mediated Gene Silencing of Human Biliverdin Reductase, but Not That of Heme Oxygenase-1, Attenuates Arsenite-mediated Induction of the Oxygenase and Increases Apoptosis in 293A Kidney Cells

“…8) places the reductase in the position of having a direct role in influencing not only HO-1 gene expression but rather influencing that of an extended list of stressresponsive genes. In the case of c-Jun, because it can form a DNA complex as a homodimer or a heterodimer not only with c-Fos but also with ATF-2/CREB (54,67,68), a change in the expression and activation state of c-Jun predictably would alter the profile of the cell signaling pathways. The fact that the knock down of BVR augmented cell killing activity of arsenite is clearly consistent with the role of the reductase in the expression of genes that affect cell growth and proliferation.…”

The Nuclear Import of Oncoprotein Hepatitis B X-interacting Protein Depends on Interacting with c-Fos and Phosphorylation of Both Proteins in Breast Cancer Cells

“…Plasmids and siRNAs-pCMV-3V-c-Fos, pCMV-4A-c-Fos, and full-length HBXIP constructs were previously described (6,27,28). To identify the corresponding domain that activates c-Fos, full-length HBXIP was divided into 4 fragments, including amino acids 1-82, 83-173, 83-144, and 145-173.…”

The mammalian Jun proteins: redundancy and specificity

“…These proteins are characterized by a highly charged, basic DNA binding domain, immediately adjacent to an amphipathic dimerization domain, referred as the`Leucine zipper' (Kouzarides and Zi , 1988;Landschulz et al, 1988). Dimerization is required for speci®c and high a nity binding to the palindromic DNA sequence, TGAC/GTCA (Rauscher et al, 1988;Gentz et al, 1989;Ransone et al, 1989;Schuermann et al, 1989;Turner and Tjian, 1989). The di erent AP-1 dimers exhibit similar DNA binding speci®cities but di er in their transactivation e ciencies (Chiu et al, 1989;Kerppola and Curran, 1991b;Suzuki et al, 1991).…”