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A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the AP1 binding site

Abstract

THE TPA (12-O-tetradecanoyl-phorbol-13-acetaie) responsive element (TRE) is recognized by the inducible transcription factor AP1, a heterodimeric complex of Fos- and Jun-protein subunits, which each contain a specific structure known as the leucine zipper through which they interact1–7. Studies using site-directed mutagenesis have shown that a basic region adjacent to the leucine zipper in Fos is crucial for the interaction of the Fos–Jun complex with the TRE, and probably represents a site of interaction with DNA. The functionally crucial amino acids in this region are almost completely conserved between Fos and Jun (refs 6, 7 and 11; M.N. and R.M., unpublished results), indicating the formation of a nearly symmetrical DNA-binding site in the Fos–Jun complex. Whereas Jun can form a homodimeric protein complex which binds to the TRE, Fos is unable to do so. The Fos–Jun heterodimer, however, possesses at least a 30-fold-higher affinity for the TRE than does the Jun–Jun homodimer, indicating cooperative bind-ing6–11. Because Fos cannot form a homodimer it is not known whether Fos specifically recognizes part of the TRE or has a different role in the binding of the Fos–Jun complex to DNA. Here we report that exchanging the leucine zipper in Fos with that of Jun generates a protein (termed Ψ-Fos) that can form a complex with Fos. This Fos–Ψ-Fos complex, and to a lesser extent a homodimeric Ψ-Fos complex, exhibits specific binding to the TRE. This finding strongly supports the hypothesis that Fos and Jun form a nearly symmetrical DNA-binding site that interacts with the palindromic TRE.

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Neuberg, M., Adamkiewicz, J., Hunter, J. et al. A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the AP1 binding site. Nature 341, 243–245 (1989). https://doi.org/10.1038/341243a0

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