Fos-Jun heterodimer

Kerppola, T. K. Curran, T. Fos-Jun heterodimers and Jun homodimers bend DNA in opposite orientations implications for transcriptional factor cooperatively. Cell 1991 66 317-326. 

The oncogene of the FBJ murine osteosarcoma virus (fos) codes for a related nuclear protein that participates in transcriptional regulation. In human fibroblasts the fos protein is mostly associated with c-jun. The fos-jun complex binds specifically to DNA. Since fos alone does not show specific DNA binding, it is believed that jun is responsible for this affinity. Although jun can form homodimers that bind to DNA, the heterodimers formed between fos and jun show a greater affinity. The heterodimers are also more effective in transcription activation therefore the heterodimer is probably the functionally relevant state of the jun and fos proteins. 

The structure of the heterodimeric transcription factor Fos/Jun bound to DNA has been solved. Jun contains a basic leucine zipper (bZIP) motif. Formation of a stable heterodimer is necessary for binding to DNA (see below). 

Circular permutation and phase-sensitive gel electrophoretic analyses by Kerppola and Curran indicate that Fos and Jun heterodimers bend DNA in the direction of the minor groove [22,25,20], The bend is inclined towards... 

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

DNA-binding proteins. A whole series of oncogenes code for transcription factors. Particularly important for cell proliferation are myc, as well as fos and jun. The protein products of the latter two genes form the transcription factor AP-1 as a heterodimer (see p. 244). 

Fig. 1.39. Examples for families of interacting transcription factors. The circles indicate groups of eucaryotic transcription factors that can form homo- and heterodimers amongst themselves. The intersection of the circle of the ATT family with the circle of the Jun family indicates possible heterodimerization between the two famihes. The members of the Jun family can form complexes with members of the Fos family and with the members of the ATT family. The Fos family is unique in that its members can not form homodimers, but must heterodimerize with members of the Jun family. C/EBP CCAAT/enhancer binding protein ATF activating transcription factor CRE-BP cAMP responsive element binding protein. After Lamb and McKnight (1992).

Each of the monomeric proteins c-jun and c-fos, as well as other members of the leucine zipper family, has an N-terminal DNA-binding domain rich in positively charged basic amino acid side chains, an activation domain that can interact with other proteins in the initiation complex, and the leucine-rich dimerization domain.363 The parallel coiled-coil structure (Fig. 2-21) allows for formation of either homodimers or heterodimers. However, cFos alone does not bind to DNA significantly and the cjun/cFos heterodimer binds much more tightly than does cjun alone.364 The yeast transcriptional activator protein GCN4 binds to the same 5 -TGACTCA sequence as does the mammalian AP-1 and also has a leucine zipper structure.360 364 365... 

Kataoka K, Noda M, Nishizawa M. 1994. Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol Cell Biol 14 700-712. 

Since each monomer of the Jun/Fos heterodimer can be phosphorylated separately, each can make an independent contribution to the transcriptional activity of the complex. For example, exclusive phosphorylation of a single threonine, Thr232, located in the N-terminal region of Jun by JNK (the Jun amino-terminal kinase), gives a characteristic and specific stress response. 

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