Jun transcription factor

FIGURE 2—38. How early genes activate late genes, part 3. Once Fos and Jun proteins are synthesized, they can collaborate as partners and produce a Fos-Jun combination protein, which now acts as a transcription factor for late genes. Sometimes the Fos-Jun transcription factor is called a leucine zipper. 

C-Jun-N-terminal kinases The JNK/Stress-activated protein kinases (SAPKs) do not respond well to mitogens but are strongly activated by agents that induce cellular stress. These kinases phosphorylate C-Jun transcription factor. The sequence of the tripeptide motif for JNK is Thr-Pro-Tyr. The activators of cytokine and tyrosine kinase receptors transduce signal to the upstream MAPKKKs. These... 

Schlingensiepen, K.H., F. Wollnik, M. Kunst, R. Schlingensiepen, T. Herdegen, and W. Brysch (1994). The role of Jun transcription factor expression and phosphorylation in neuronal differentiation, neuronal cell death, and plastic adaptations in vivo. Cell. Mol. Neurobiol. 14 487-505. 

Bonetti B, Stegagno C, CanneUa B, Rizzuto N, Moreno G et al (1999) Activation of NF-kappaB and c-jun transcription factors in multiple sclerosis lesions. Implications for oligodendrocyte pathology. Am J Pathol 155 1433-1438... 

The mode of action of Smad 4 clearly differs from that of the other members of the Smad family. Smad 4 binds to phosphorylated R-Smads and forms trimeric complexes composed of two R-Smad molecules and one Smad 4 molecule. These complexes translocate to the nucleus, where they bind to related DNA elements and activate the transcription of target genes. The mechanism of transcription regulation by Smads is complex and includes both positive and negative influences. Generally, Smad-dependent regulation of transcription requires the interaction with other transcription factors, such as members of the FoxH 1 family of forkhead transcription factors, the Vitamin D receptor and the c-Jun transcription factor, among others (review Attisano et al., 2001). Futhermore, Smads can interact with coactivators and corepressors of transcription and thereby recruit, e. g., histone acetylase activity or histone deacetylase activity to chromatin. 

Xie, W.. and Herschman. H.R. (1995) v-Src Induces Prostaglandin Synthase 2 Gene Expression by Activation of the c-Jun N-Terminal Kinase and the c-Jun Transcription Factor, J. Biol. Chem. 270,27622-276228. 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

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. 

Glover, J.N.M., Harrison, S.C. Crystal structure of the het-erodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 373 257-261, 1995. 

Activator Protein-1 (API) comprises transcriptional complexes formed by dimers of members oftheFos, Jun, and ATF family of transcription factors. These proteins contain basic leucine zipper domains that mediate DNA binding and dimerization. They regulate many aspects of cell physiology in response to environmental changes. 

Immediate early genes, e.g., c-fos, c-jun, and c-myc, are the first genes whose expression is induced in cells after a growth stimulus. They encode transcription factors and induce the expression of other growth-related genes. 

TAK-1 can also activate c-jun N-terminal kinase ( JNK) andp38 both of which are MAP kinases. JNK activates the transcription factor AP-1 and p38 is involved in mRNA stabilisation. This pathway is also capable of activating ERF-7 in dendritic cells in response to TLR-7 and TLR-9 ligands. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

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