From Proteopedia

Revision as of 05:43, 1 April 2010

Andrew Rebeyka

C-JUN

Introduction

The c-Jun protein is a member of transcription factors which consist of a basic region leucine zipper region ^[1] PMID:8662824 </ref>. Originally identified by its homology to v-jun, the oncogene from the avian sarcomoa virus.^[2] Bossy-Wetzel, E., Bakiri, L., Yaniv, M. (1997). Induction of apoptosis by the transcription factor c-Jun. EMO Journal. Vol.16;7. 1695-1709 </ref>. All these leucine zipper factors bind to DNA in one of two states: homo or heterodimers ^[1]. In conjunction with the c-Fos protein these two proteins bind to specific regions of DNA strands. Together these two proteins form the c-fos/c-jun complex which help regulate cell growth and differentiation ^[1]. the members of the jun and fos families include three Jun proteins and four Fos proteins (c-Jun, JunB, JunD,c-Fos, Fos-B, Fra1, and Fra2) ^[3] PMID:12798298 </ref>. Regulation of the complex iteslf is done by interactions between the protein and DNA in addition to the protein-protein interactions between each of the leucine zipper domains ^[1].

Structure Overview

The structure of c-Jun is comprised of a leucine zipper as previously stated. This dimerization motif may be in one of two classes, both of which are required for DNA-binding transcription factors; the basic-domain leucine zipper proteins (bZIP) and the basic helix loop-helix-leucine zipper proteins(bHLH-ZIP) ^[5] A Junius, F.K., Mackay, J.P., Bubb, W.A., Jensen, S.A., Weiss, A.S., King, G.F. 2006. Nuclear Magnetic Resonance Characterization of the Jun Leucine Zipper Domain: Unusual Properties of Coiled-Coil Interfacial Polar Residues?</ref>. As can be been in the figure XXXXX, the strand becomes an elongated coiled coil. This is formed by residues at the a and d positions in each of the two monomers, whereby they create hydrophobic centers which conform to the "knobs into holes" model by Crick. ^[5]. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer ^[5].

the a and d residues each exhibit varying types of packing in terms of this "knobs into holes" theory. According to Harbury et al.(24) the leucines at the a positions are packed "parallel" in such a way that the C-alpha-C-beta bond vector lies in a parallel manner to the C-alpha-C-alpha vector at the base of the acceptor hole on adjacent helix ^[1]. Whereas the opposite is true for the leucines in the d positions. Here the residues are packed in a "perpendicular" nature ^[1]. The bond vector of the C-alpha-C-beta pack approximately perpendicular to the C-alpha-C-alpha vector at the base of the hole of the second helix in which it packs ^[1]. therefore only the leucine side chains in the a positions, which point away from the boundary, make van der Waals interactions ^[1].

This protein is a dimer that is completely symmetrical ^[5]. It is comprised of a coiled coil of two alpha helices ^[5].

C-Jun binds to specific DNA sites either in the homodimer or heterodimer forms with the aid of C-Fos protein ^[1]. C-Jun is a transcriptional activator ^[1]. C-jun, with the aid of C-Fos represents a crucial union between normal and uncontrolled cell growth as their combined role in the transduction of afferent growth signals the response of specific genes ^[1].

Protein Function

The primary function of c-Jun is in regards to DNA transcription. Specifically, the protein is involved in proliferation, apoptosis, oncogenic transformation and various cellular processes ^[3]. for instance cells which lack an allele for c-jun show stunted growth both in vitro and in vivo ^[2]. whereas a prolonged and therefore strong induction of c-jun has been in response to such things as tumor necrosis factor, stress inducing stimuli such as UV ^[2].

Protein Regulation

OTHER

The stress-induced signalling cascade may also active c-Jun by phosphorylation. the N-ternminal protein kinase phosphorylates Ser63 and Ser73 ^[6] PMID:10064599 </ref> . Another mechanism for the activation however is interestingly through intracellular calcium concentrations. increasing these concentrations by opening the L-type voltage gated calcium channels It was found that the N-terminus contains both calcium and stress-regulated transcriptional activation domains ^[6]. According to the study,distinct mechanisms of c-Jun control function by calcium and stress signals ^[6].

References

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