C-JUN

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Human C-Jun homodimer leucine zipper domain complex with acetyl (PDB code 1jun)

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1 Introduction
2 Structure Overview
3 Protein Function
4 Protein Regulation
5 Psychological Influences
6 Additional Resources

Introduction

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 ^[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) ^[1]. 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]. See Transcription and RNA Processing.

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) ^[3]. 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 ^[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].

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 ^[4]. For instance cells which lack an allele for c-jun have been shown to stunt 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 or stress inducing stimuli such as ultra violet radiation ^[2].

Protein Regulation

Changes made in the phosphorylation state of specific amino acids is one means by which c-Jun regulates transcription ^[5]. 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 ^[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 dephsphorylation of these three residues occurs.

Psychological Influences

The stress-induced signaling cascade may also active c-Jun by phosphorylation. The N-ternminal protein kinase phosphorylates Ser63 and Ser73 ^[6] . Another mechanism for the activation however is interestingly through intracellular calcium concentrations. Increasing these concentrations by opening the L-type voltage gated calcium channels leads to serines phosphorlation. 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].

Additional Resources

To See Additional information, see: Transcription and RNA Processing

3D structure of C-JUN

Updated on 11-April-2018

1jun – hCJUN leucine zipper domain – human – NMR
1jnm - hCJUN leucine zipper domain + DNA
1fos – hCJUN + p55 c-Fos + DNA
5fv8 – hCJUN + FOSW

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 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 ^3.3 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
↑ Mechta-Grigoriou F, Giudicelli F, Pujades C, Charnay P, Yaniv M. c-jun regulation and function in the developing hindbrain. Dev Biol. 2003 Jun 15;258(2):419-31. PMID:12798298
↑ ^5.0 ^5.1 ^5.2 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
↑ ^6.0 ^6.1 ^6.2 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

Proteopedia Page Contributors and Editors (what is this?)

Andrew Rebeyka, Michal Harel, Alexander Berchansky, David Canner, Andrea Gorrell

Retrieved from "http://52.214.119.220/wiki/index.php/C-JUN"

Category: Topic Page

@@ Line 1: / Line 1: @@
-Andrew Rebeyka
+<StructureSection load='1jun' size='350' side='right' scene='' caption='Human C-Jun homodimer leucine zipper domain complex with acetyl (PDB code [[1jun]])'>
-= '''C-JUN''' =
-----
-<applet load='1Z82' size='200' frame='true' align='right' caption='1JUN' />
 == 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="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">.
+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]].
 == Structure Overview ==
-[[Image:1jun.png|left|thumb|'''Figure 1.''' A 3-D representation of the two alpha helices which form a coiled coil [http://www.rcsb.org/pdb/explore/jmol.do?structureId=1JUN]]]
+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 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 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 ==
-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"/>.
+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" />.
 == Protein Regulation ==
-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.
+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.
 == Psychological Influences ==
 The stress-induced signaling cascade may also active c-Jun by phosphorylation.  The N-ternminal protein kinase phosphorylates Ser63 and Ser73 <ref name="five"> 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 leads to serines phosphorlation.
-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"/>.
+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" />.
+==Additional Resources==
+To See Additional information, see: [[Transcription and RNA Processing]] <br />
+</StructureSection>
+==3D structure of C-JUN==
+Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+[[1jun]] – hCJUN leucine zipper domain – human – NMR<br />
+[[1jnm]] - hCJUN leucine zipper domain + DNA<br />
+[[1fos]] – hCJUN + p55 c-Fos + DNA<br />
+[[5fv8]] – hCJUN + FOSW<br />
 == References ==
 <references/>
+[[Category:Topic Page]]

C-JUN

From Proteopedia

Current revision

Contents

Introduction

Structure Overview

Protein Function

Protein Regulation

Psychological Influences

Additional Resources

3D structure of C-JUN

References

Proteopedia Page Contributors and Editors (what is this?)

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