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Gene Review

GADD45G  -  growth arrest and DNA-damage-inducible, gamma

Homo sapiens

Synonyms: CR6, Cytokine-responsive protein CR6, DDIT-2, DDIT2, DNA damage-inducible transcript 2 protein, ...
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Disease relevance of GADD45G


High impact information on GADD45G


Biological context of GADD45G


Anatomical context of GADD45G

  • The MyD118, CR6, and GADD45 proteins were shown to predominantly localize within the cell nucleus [12].
  • Only one single sequence change in the coding region was detected in 1 of 25 cell lines examined, indicating that genetic inactivation of GADD45G is very rare [10].
  • Same as other GADD45 members, GADD45G is ubiquitously expressed in all normal adult and fetal tissues [10].
  • However, E-selectin containing all six CR domains (Lec-EGF-CR6) at its COOH terminus was the most potent in blocking neutrophil or HL-60 cell adhesion to either immobilized E-selectin or cytokine-stimulated human umbilical vein endothelial cells [13].
  • In addition, the adenovirus-mediated reexpression of Gadd45gamma significantly inhibited the proliferation of anaplastic thyroid carcinoma cells, ARO, FRO, and NPA cells, which was attributed to apoptosis [14].

Associations of GADD45G with chemical compounds


Physical interactions of GADD45G


Co-localisations of GADD45G


Other interactions of GADD45G

  • Importantly, evidence has been obtained that interaction of CR6 with PCNA impedes the function of this protein in negative growth control, similar to observations reported for MyD118 and GADD45 [12].
  • Data accumulated suggest that MyD118/GADD45/CR6 serve similar but not identical functions along different apoptotic and growth suppressive pathways [12].
  • A mutant with a deletion of the central region (residues 50-76), which is conserved in the family members GADD45beta and GADD45gamma, lacked such activity [18].
  • The silencing of GADD45G could be reversed by 5-aza-2'-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism [10].
  • In the present study, following clone and location of human GADD45 gamma (MyDL) gene, we have found that its mRNA expression level was down-regulated in 15/23 cases of clinic hepatocellular carcinoma (HCC) by comparing the northern hybridization results between the tumor tissues and adjacent normal tissues [2].

Analytical, diagnostic and therapeutic context of GADD45G


  1. Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. Fan, W., Richter, G., Cereseto, A., Beadling, C., Smith, K.A. Oncogene (1999) [Pubmed]
  2. GADD45gamma, down-regulated in 65% hepatocellular carcinoma (HCC) from 23 chinese patients, inhibits cell growth and induces cell cycle G2/M arrest for hepatoma Hep-G2 cell lines. Sun, L., Gong, R., Wan, B., Huang, X., Wu, C., Zhang, X., Zhao, S., Yu, L. Mol. Biol. Rep. (2003) [Pubmed]
  3. Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis. Zhang, X., Sun, H., Danila, D.C., Johnson, S.R., Zhou, Y., Swearingen, B., Klibanski, A. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  4. Gadd45gamma is androgen-responsive and growth-inhibitory in prostate cancer cells. Jiang, F., Wang, Z. Mol. Cell. Endocrinol. (2004) [Pubmed]
  5. GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells. Lu, B., Yu, H., Chow, C., Li, B., Zheng, W., Davis, R.J., Flavell, R.A. Immunity (2001) [Pubmed]
  6. GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cells. Chi, H., Lu, B., Takekawa, M., Davis, R.J., Flavell, R.A. EMBO J. (2004) [Pubmed]
  7. mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK. Sarkar, D., Su, Z.Z., Lebedeva, I.V., Sauane, M., Gopalkrishnan, R.V., Valerie, K., Dent, P., Fisher, P.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. A novel pathway involving melanoma differentiation associated gene-7/interleukin-24 mediates nonsteroidal anti-inflammatory drug-induced apoptosis and growth arrest of cancer cells. Zerbini, L.F., Czibere, A., Wang, Y., Correa, R.G., Otu, H., Joseph, M., Takayasu, Y., Silver, M., Gu, X., Ruchusatsawat, K., Li, L., Sarkar, D., Zhou, J.R., Fisher, P.B., Libermann, T.A. Cancer Res. (2006) [Pubmed]
  9. Gadd45 proteins induce G2/M arrest and modulate apoptosis in kidney cells exposed to hyperosmotic stress. Mak, S.K., Kültz, D. J. Biol. Chem. (2004) [Pubmed]
  10. The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Ying, J., Srivastava, G., Hsieh, W.S., Gao, Z., Murray, P., Liao, S.K., Ambinder, R., Tao, Q. Clin. Cancer Res. (2005) [Pubmed]
  11. Assignment of human GADD45G to chromosome 9q22.1-->q22.3 by radiation hybrid mapping. Gong, R., Yu, L., Zhang, H., Tu, Q., Zhao, Y., Yang, J., Xu, Y., Zhao, S. Cytogenet. Cell Genet. (2000) [Pubmed]
  12. Interaction of CR6 (GADD45gamma ) with proliferating cell nuclear antigen impedes negative growth control. Azam, N., Vairapandi, M., Zhang, W., Hoffman, B., Liebermann, D.A. J. Biol. Chem. (2001) [Pubmed]
  13. Consensus repeat domains of E-selectin enhance ligand binding. Li, S.H., Burns, D.K., Rumberger, J.M., Presky, D.H., Wilkinson, V.L., Anostario, M., Wolitzky, B.A., Norton, C.R., Familletti, P.C., Kim, K.J. J. Biol. Chem. (1994) [Pubmed]
  14. Gadd45gamma expression is reduced in anaplastic thyroid cancer and its reexpression results in apoptosis. Chung, H.K., Yi, Y.W., Jung, N.C., Kim, D., Suh, J.M., Kim, H., Park, K.C., Kim, D.W., Hwang, E.S., Song, J.H., Ku, B.J., Han, H.J., Ro, H.K., Kim, J.M., Shong, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  15. Ectopic expression of MyD118/Gadd45/CR6 (Gadd45beta/alpha/gamma) sensitizes neoplastic cells to genotoxic stress-induced apoptosis. Zhang, W., Hoffman, B., Liebermann, D.A. Int. J. Oncol. (2001) [Pubmed]
  16. Regulation of Gadd45gamma expression by C/EBP. Jung, N., Yi, Y.W., Kim, D., Shong, M., Hong, S.S., Lee, H.S., Bae, I. Eur. J. Biochem. (2000) [Pubmed]
  17. CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle. Chung, H.K., Yi, Y.W., Jung, N.C., Kim, D., Suh, J.M., Kim, H., Park, K.C., Song, J.H., Kim, D.W., Hwang, E.S., Yoon, S.H., Bae, Y.S., Kim, J.M., Bae, I., Shong, M. J. Biol. Chem. (2003) [Pubmed]
  18. Identification of a functional domain in a GADD45-mediated G2/M checkpoint. Yang, Q., Manicone, A., Coursen, J.D., Linke, S.P., Nagashima, M., Forgues, M., Wang, X.W. J. Biol. Chem. (2000) [Pubmed]
  19. Molecular cloning, expression, and mapping of a novel human cDNA, GRP17, highly homologous to human gadd45 and murine MyD118. Suzuki, M., Watanabe, T.K., Fujiwara, T., Nakamura Yp6, n.u.l.l., Takahashi, E., Tanigami, A. J. Hum. Genet. (1999) [Pubmed]
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