# Gadd45
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The '''Growth Arrest and DNA Damage''' or '''''gadd45''''' [gene](/source/gene)s, including [GADD45A](/source/GADD45A) (originally termed gadd45) [GADD45B](/source/GADD45B) (originally termed MyD118), and [GADD45G](/source/GADD45G) (originally termed CR6), are implicated as stress sensors that modulate the response of [mammal](/source/mammal)ian [cells](/source/cell_(biology)) to [genotoxic](/source/Genotoxicity)/[physiological stress](/source/Stress_(biological)), and modulate [tumor](/source/tumor) formation. Gadd45 [protein](/source/protein)s interact with other proteins implicated in stress responses, including [PCNA](/source/PCNA), [p21](/source/p21), [Cdc2](/source/Cdc2)/CyclinB1, [MEKK4](/source/MEKK4), and [p38 kinase](/source/p38_kinase).[{{cite journal|author1=Fornace, A.J. |author2=Jackman, J. |author3=Hollander, M.C. |author4=Hoffman-Liebermann, B. |author5=Liebermann, D.A. |title=Genotoxic-stress-response genes and growth-arrest genes: gadd, MyD, and other genes induced by treatments eliciting growth arrest|journal=Annals of the New York Academy of Sciences|volume=663|pages=139–53|year=1992|pmid=1482047|doi=10.1111/j.1749-6632.1992.tb38657.x|s2cid=37885339 }}][{{cite journal|author=Liebermann, D.A.|author2=Hoffman, B.|title=Myeloid differentiation (MyD)/growth arrest DNA damage (GADD) genes in tumor suppression, immunity and inflammation|journal=Leukemia|volume=16|issue=4|pages=527–41|year=2002|pmid=11960329|doi=10.1038/sj.leu.2402477|doi-access=}}]
GADD45 proteins regulate [differentiation](/source/cellular_differentiation) at the two cell stage of [embryogenesis](/source/embryonic_development), a key stage of [zygotic genome activation](/source/zygotic_genome_activation).[Schüle KM, Leichsenring M, Andreani T, Vastolo V, Mallick M, Musheev MU, Karaulanov E, Niehrs C. GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells. Genes Dev. 2019 Jul 1;33(13-14):782-798. doi: 10.1101/gad.325696.119. Epub 2019 Jun 6. PMID 31171699] GADD45 likely acts by promoting [TET](/source/TET_enzymes)-mediated [DNA demethylation](/source/DNA_demethylation) leading to the induction of [expression of genes](/source/gene_expression) necessary for zygote activation.
Overexpression of the ''GADD45'' gene in the ''[Drosophila melanogaster](/source/Drosophila_melanogaster)'' [nervous system](/source/nervous_system) significantly increases [longevity](/source/longevity).[Plyusnina EN, Shaposhnikov MV, Moskalev AA. Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system. Biogerontology. 2011 Jun;12(3):211-26. doi: 10.1007/s10522-010-9311-6. Epub 2010 Dec 9. PMID 21153055] This longevity increase can be attributed to more efficient recognition and repair of [spontaneous DNA damages](/source/DNA_damage_(naturally_occurring)) generated by physiological processes and environmental factors.
== History ==
*[Gadd45a](/source/Gadd45a) was discovered and characterized in the laboratory of Dr. [Albert J. Fornace Jr.](/source/Albert_J._Fornace_Jr.) in 1988.[{{cite journal|author=Fornace, A.J.|author2=Alamo, I. |author3= Hollander, M.C. |title=DNA damage-inducible transcripts in mammalian cells|journal=Proceedings of the National Academy of Sciences|volume=85|issue=23|pages=8800–4|year=1988|pmid=3194391|doi=10.1073/pnas.85.23.8800|pmc=282594|bibcode=1988PNAS...85.8800F |doi-access=free }}]
*[Gadd45b](/source/Gadd45b) (MyD118) was discovered and characterized in the laboratories of Drs. [Dan A. Liebermann](/source/Dan_A._Liebermann) and Barbara Hoffman in 1991.[{{cite journal|author=Abdollahi, A.|author2=Lord, K.A. |author3=Hoffman-Liebermann, B. |author4= Liebermann, D.A. |title=Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines|journal=Oncogene|volume=6|issue=1|pages=165–7|year=1991|pmid=1899477}}]
*[Gadd45g](/source/Gadd45g) (CR6) was discovered and characterized in the laboratories of Drs. Kenneth Smith, Dan A. Liebermann, and Barbara Hoffman in 1993 and 1999.[{{cite journal|author=Zhang, W.|title=CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control|journal=Oncogene|volume=18|issue=35|pages=4899–907|year=1999|pmid=10490824|doi=10.1038/sj.onc.1202885|last2=Bae|first2=I.|last3=Krishnaraju|first3=K.|display-authors=4|last4=Azam|first4=Naiyer|last5=Fan|first5=Wen|last6=Smith|first6=Kendall|last7=Hoffman|first7=Barbara|last8=Liebermann|first8=Dan A|doi-access=}}][{{cite journal|author1=Beadling, C. |author2=Johnson, K.W. |author3=Smith, K.A. |title=Isolation of interleukin 2-induced immediate-early genes|journal=Proceedings of the National Academy of Sciences|volume=90|issue=7|pages=2719–23|year=1993|pmid=7681987|doi=10.1073/pnas.90.7.2719|pmc=46167|bibcode=1993PNAS...90.2719B |doi-access=free }}]
== See also ==
* [GADD45A](/source/GADD45A)
* [GADD45B](/source/GADD45B)
* [GADD45G](/source/GADD45G)
== References ==
{{reflist}}
== External links ==
* {{MeshName|GADD45+protein}}
Category:Mammal genes
{{biochem-stub}}
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Adapted from the Wikipedia article [Gadd45](https://en.wikipedia.org/wiki/Gadd45) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Gadd45?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.