C-JUN: Difference between revisions
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== Introduction == | == Introduction == | ||
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=" | 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>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">. | ||
== Structure Overview == | == Structure Overview == | ||
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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="ref2"/> 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. <ref name="ref2"/>. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer <ref name="ref2"/>. | 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="ref2"/> 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. <ref name="ref2"/>. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer <ref name="ref2"/>. | ||
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=" | 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">. | ||
== Protein Function == | == Protein Function == | ||
Revision as of 09:38, 1 April 2010
Andrew Rebeyka
C-JUNC-JUN
|
IntroductionIntroduction
The c-Jun protein is a member of transcription factors which consist of a basic region leucine zipper region [1]. 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 [3]. 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 Cite error: Closing </ref> missing for <ref> tag. 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. [4]. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer [4].
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 Cite error: Closing </ref> missing for <ref> tag. To date two seperate sites of phosphorylation have been identified. at the N-terminal end are the amino acids Ser63 and Ser73, which are phosphorylated in response to ras expression. When ras is expressed, and Ser63 and Ser73 are phosphorylated, 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 [5]. Unlike the two serines at the N-terminal end, phosphorylation at the C-terminal end inhibits DNA binding to c-Jun [5]. therefore with the expression of such oncogenes as ras lead to dephsphorylation of these three residues.
Psychological InfluencesPsychological Influences
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].
ReferencesReferences
- ↑ Junius FK, O'Donoghue SI, Nilges M, Weiss AS, King GF. High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer. J Biol Chem. 1996 Jun 7;271(23):13663-7. PMID:8662824
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedfour - ↑ Junius FK, O'Donoghue SI, Nilges M, Weiss AS, King GF. High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer. J Biol Chem. 1996 Jun 7;271(23):13663-7. PMID:8662824
- ↑ 4.0 4.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedref2 - ↑ 5.0 5.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedref6 - ↑ 6.0 6.1 6.2 Cite error: Invalid
<ref>tag; no text was provided for refs namedref5