C-JUN
Andrew Rebeyka
C-JUNC-JUN
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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]. 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. [3]. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer [3].
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. 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 RegulationProtein Regulation
Changes made in the phosphorylation state of specific amino acids is one means by which c-Jun regulates transcription [4]. 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 [4]. Unlike the two serines at the N-terminal end, phosphorylation at the C-terminal end inhibits DNA binding to c-Jun [4]. 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 [5] . 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 [5]. According to the study,distinct mechanisms of c-Jun control function by calcium and stress signals [5].
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
- ↑ 2.0 2.1 2.2 Bossy-Wetzel, E., Bakiri, L., Yaniv, M. (1997). Induction of apoptosis by the transcription factor c-Jun. EMO Journal. Vol.16;7. 1695-1709
- ↑ 3.0 3.1 3.2 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 4.2 Hoeffler WK, Levinson AD, Bauer EA. Activation of c-Jun transcription factor by substitution of a charged residue in its N-terminal domain. Nucleic Acids Res. 1994 Apr 11;22(7):1305-12. PMID:8165146
- ↑ 5.0 5.1 5.2 Cruzalegui FH, Hardingham GE, Bading H. c-Jun functions as a calcium-regulated transcriptional activator in the absence of JNK/SAPK1 activation. EMBO J. 1999 Mar 1;18(5):1335-44. PMID:10064599 doi:10.1093/emboj/18.5.1335