C-JUN: Difference between revisions

The '''c-Jun''' protein is a member of transcription factors which consist of a basic region leucine zipper region  <ref name="one"> PMID:8662824 </ref>.  Originally identified by its homology to v-jun, the oncogene from the avian sarcomoa virus <ref name="four"> 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  <ref name="two"> PMID:8662824 </ref>.  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 <ref name="one" />.  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) <ref name="one" />.  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 <ref name="one" />. See [[Transcription and RNA Processing]].       

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) <ref name="two"> 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>.  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.  <ref name="two" />.  Amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer <ref name="two" />.

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 <ref name="one" />.  Whereas the opposite is true for the leucines in the d positions.  Here the residues are packed in a "perpendicular" nature <ref name="one" />.  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 <ref name="one" />.  Therefore only the leucine side chains in the a positions, which point away from the boundary, make van der Waals interactions <ref name="one" />.         

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 <ref name="three"> PMID:12798298 </ref>.  For instance cells which lack an allele for c-jun have been shown to stunt growth both in vitro and in vivo <ref name="four" />.  Whereas a prolonged and therefore strong induction of c-jun has been in response to such things as tumor necrosis factor or stress inducing stimuli such as ultra violet radiation <ref name="four" />.         

Changes made in the phosphorylation state of specific amino acids is one means by which c-Jun regulates transcription <ref name="six"> PMID:8165146 </ref>.  To date two seperate sites of phosphorylation have been identified.  One is located at the N-terminal end in which the amino acids Ser63 and Ser73 are phosphorylated in response to ''ras'' expression.  When ''ras'' is expressed, and Ser63 and Ser73 are phosphorylated,and transcriptional activity of c-Jun increases.  The second site is located at the C-terminal which is very close in proximity to the DNA binding domain.  Here the residues are Thr214, Ser226, and Ser 232 <ref name="six" />.  Unlike the two serines at the N-terminal end, phosphorylation at the C-terminal end inhibits DNA binding to c-Jun <ref name="six" />.  Therefore with the expression of such oncogenes as ''ras''  dephsphorylation of these three residues occurs.               

It was found that the N-terminus contains both calcium and stress-regulated transcriptional activation domains <ref name="five" />.  According to the study,distinct mechanisms of c-Jun control function by calcium and stress signals <ref name="five" />.