The Growth Arrest and DNA Damage or gadd45 genes, including GADD45A (originally termed gadd45) GADD45B (originally termed MyD118), and GADD45G (originally termed CR6), are implicated as stress sensors that modulate the response of mammalian cells to genotoxic/physiological stress, and modulate tumor formation. Gadd45 proteins interact with other proteins implicated in stress responses, including PCNA, p21, Cdc2/CyclinB1, MEKK4, and p38 kinase.[1][2]
GADD45 proteins regulate differentiation at the two cell stage of embryogenesis, a key stage of zygotic genome activation.[3] GADD45 likely acts by promoting TET-mediated DNA demethylation leading to the induction of expression of genes necessary for zygote activation.
Overexpression of the GADD45 gene in the Drosophila melanogaster nervous system significantly increases longevity.[4] This longevity increase can be attributed to more efficient recognition and repair of spontaneous DNA damages generated by physiological processes and environmental factors.
^Fornace, A.J.; Jackman, J.; Hollander, M.C.; Hoffman-Liebermann, B.; Liebermann, D.A. (1992). "Genotoxic-stress-response genes and growth-arrest genes: gadd, MyD, and other genes induced by treatments eliciting growth arrest". Annals of the New York Academy of Sciences. 663: 139–53. doi:10.1111/j.1749-6632.1992.tb38657.x. PMID 1482047. S2CID 37885339.
^Liebermann, D.A.; Hoffman, B. (2002). "Myeloid differentiation (MyD)/growth arrest DNA damage (GADD) genes in tumor suppression, immunity and inflammation". Leukemia. 16 (4): 527–41. doi:10.1038/sj.leu.2402477. PMID 11960329.
^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
^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
The Growth Arrest and DNA Damage or gadd45 genes, including GADD45A (originally termed gadd45) GADD45B (originally termed MyD118), and GADD45G (originally...
(November 1995). "Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA". Oncogene. 11...
GADD45B has been shown to interact with: ASK1, GADD45GIP1, MAP2K7 and MAP3K4. Gadd45 GRCh38: Ensembl release 89: ENSG00000099860 – Ensembl, May 2017 GRCm38:...
DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene. This gene is a member of a group of genes, the GADD45 genes, whose...
CDK1 is directly inhibited by three transcriptional targets of p53: p21, Gadd45, and 14-3-3σ. Inactive Cyclin B1/CDK1 is sequestered in the nucleus by p21...
Blanck P, Roller P, Fornace AJ, Zhan Q (July 2000). "The central region of Gadd45 is required for its interaction with p21/WAF1". Exp. Cell Res. 258 (1):...
of melanocytes through reactive oxygen species-dependent activation of GADD45. It is now well established that rhododendrol is a potent tyrosinase inhibitor...
Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also...
demethylation. A role for GADD45 has also recently been indicated, since GADD45 physically interacts with thymine-DNA glycosylase (TDG) and GADD45 may promote the...
receptor (AR) locus and the growth arrest and DNA-damage-inducible protein GADD45 gamma (GADD45G) locus suggest a role in deletions that affect regulatory...
JM, Bae I, Shong M (Jul 2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". The Journal of Biological...
Bubici C, Jayawardena S, Alvarez K, Matsuda S, et al. (February 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting...
M, Wang XW (November 2000). "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". J. Biol. Chem. 275 (47): 36892–8. doi:10.1074/jbc...
2017). "3 enhances TRPV6 transcription through p38 MAPK activation and GADD45 expression". The Journal of Steroid Biochemistry and Molecular Biology....
kinase 4". Takekawa, M; Saito H (Nov 1998). "A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK"...
Growth Arrest and DNA Damage inducible 45 (Gadd45) gene family plays a large role in the hippocampus. Gadd45 facilitates hippocampal long-term potentiation...
S2CID 28576187. Fan W, Jin S, Tong T, et al. (March 2002). "BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs". The Journal of...
C, Shindo N, Furuichi K, Sakai T (2003). "p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription...
PMID 10490659. Papa S, Zazzeroni F, Bubici C, et al. (February 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting...
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