JunD

JUND
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3U86
Identifiers
Aliases	JUND, AP-1, JunD, JunD proto-oncogene, AP-1 transcription factor subunit
External IDs	OMIM: 165162; MGI: 96648; HomoloGene: 3910; GeneCards: JUND; OMA:JUND - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	18,281,622 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	71,153,265 bp
RNA expression pattern
	Top expressed in
	cardia; ; vena cava; ; nipple; ; paraflocculus of cerebellum; ; pylorus; ; renal medulla; ; lactiferous duct; ; trachea; ; saphenous vein; ; Brodmann area 10;
	Top expressed in
	granulocyte; ; adrenal gland; ; bone marrow; ; islet of Langerhans; ; ileum; ; ganglionic eminence; ; cerebellar cortex; ; primary visual cortex; ; striatum of neuraxis; ; urinary bladder;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	DNA binding; sequence-specific DNA binding; DNA-binding transcription factor activity; transcription coactivator activity; protein binding; enzyme binding; double-stranded DNA binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; transcription factor binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity, RNA polymerase II-specific; nuclear receptor binding;
Cellular component	protein-DNA complex; chromatin; nucleus; transcription factor AP-1 complex; protein-containing complex; nucleoplasm; transcription regulator complex;
Biological process	cellular response to calcium ion; response to cytokine; regulation of transcription, DNA-templated; response to organic cyclic compound; response to light stimulus; regulation of cell death; human ageing; response to peptide hormone; negative regulation of transcription by RNA polymerase II; transcription by RNA polymerase II; transcription, DNA-templated; regulation of cell cycle; cellular response to hormone stimulus; positive regulation of osteoblast differentiation; regulation of cell population proliferation; circadian rhythm; positive regulation of cell differentiation; osteoblast development; response to radiation; response to cAMP; response to lipopolysaccharide; response to mechanical stimulus; regulation of transcription by RNA polymerase II; positive regulation of transcription by RNA polymerase II; response to organic substance;
	Sources:Amigo / QuickGO
Orthologs
	3727
	16478
	ENSG00000130522
	ENSMUSG00000071076
	P17535
	P15066
	NM_005354; NM_001286968
	NM_001286944; NM_010592
	NP_001273897; NP_005345
	NP_001273873; NP_034722
	Wikidata
View/Edit Human	View/Edit Mouse

Transcription factor JunD is a protein that in humans is encoded by the JUND gene.^[5]^[6]

Function

The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. It has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternate translation initiation site usage results in the production of different isoforms.^[7]

ΔJunD

The dominant negative mutant variant of JunD, known as ΔJunD or Delta JunD, is a potent antagonist of the ΔFosB transcript, as well as other forms of AP-1-mediated transcriptional activity.^[8]^[9]^[10] In the nucleus accumbens, ΔJunD directly opposes many of the neurological changes that occur in addiction (i.e., those induced by ΔFosB).^[9]^[10] ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.^[11] Being an unnatural genetic variant, deltaJunD has not been observed in humans.

Interactions

JunD has been shown to interact with ATF3,^[12] MEN1,^[13] DNA damage-inducible transcript 3^[14] and BRCA1.^[15]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000130522 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000071076 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Nomura N, Ide M, Sasamoto S, Matsui M, Date T, Ishizaki R (July 1990). "Isolation of human cDNA clones of jun-related genes, jun-B and jun-D". Nucleic Acids Res. 18 (10): 3047–8. doi:10.1093/nar/18.10.3047. PMC 330838. PMID 2112242.
^ Berger I, Shaul Y (June 1991). "Structure and function of human jun-D". Oncogene. 6 (4): 561–6. PMID 1903194.
^ "Entrez Gene: JUND jun D proto-oncogene".
^ Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–98. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.
^ ^a ^b Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
^ ^a ^b Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM (October 2010). "ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward". Genes Brain Behav. 9 (7): 831–40. doi:10.1111/j.1601-183X.2010.00621.x. PMC 2970635. PMID 20618447.
^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 384–385. ISBN 9780071481274.
^ Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Mol. Endocrinol. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.
^ Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL (January 1999). "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell. 96 (1): 143–52. doi:10.1016/S0092-8674(00)80967-8. PMID 9989505. S2CID 18116746.
^ Ubeda M, Vallejo M, Habener JF (November 1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. 19 (11): 7589–99. doi:10.1128/MCB.19.11.7589. PMC 84780. PMID 10523647.
^ Hu YF, Li R (June 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC 186344. PMID 12080089.

External links

JUND+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
FactorBook JunD
PDBe-KB provides an overview of all the structure information available in the PDB for Human Transcription factor jun-D

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000130522 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000071076 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2112242-5] Nomura N, Ide M, Sasamoto S, Matsui M, Date T, Ishizaki R (July 1990). "Isolation of human cDNA clones of jun-related genes, jun-B and jun-D". Nucleic Acids Res. 18 (10): 3047–8. doi:10.1093/nar/18.10.3047. PMC 330838. PMID 2112242.

[pmid1903194-6] Berger I, Shaul Y (June 1991). "Structure and function of human jun-D". Oncogene. 6 (4): 561–6. PMID 1903194.

[entrez-7] "Entrez Gene: JUND jun D proto-oncogene".

[Nestler,_Hyman,_and_Malenka_2-8] Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–98. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597.

[Nestler-9] Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.

[Genetic_sex_addiction-10] Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM (October 2010). "ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward". Genes Brain Behav. 9 (7): 831–40. doi:10.1111/j.1601-183X.2010.00621.x. PMC 2970635. PMID 20618447.

[Malenka_2009_04-11] Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 384–385. ISBN 9780071481274.

[pmid8152431-12] Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ (January 1994). "Activating transcription factor-3 stimulates 3',5'-cyclic adenosine monophosphate-dependent gene expression". Mol. Endocrinol. 8 (1): 59–68. doi:10.1210/mend.8.1.8152431. PMID 8152431.

[pmid9989505-13] Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL (January 1999). "Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription". Cell. 96 (1): 143–52. doi:10.1016/S0092-8674(00)80967-8. PMID 9989505. S2CID 18116746.

[pmid10523647-14] Ubeda M, Vallejo M, Habener JF (November 1999). "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Mol. Cell. Biol. 19 (11): 7589–99. doi:10.1128/MCB.19.11.7589. PMC 84780. PMID 10523647.

[pmid12080089-15] Hu YF, Li R (June 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC 186344. PMID 12080089.

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