Home LiteratureArticle Details
PMID: 8139541 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth.

Molecular and cellular biology ·Vol. 14 ·No. 4 ·1994-04-00 ·Pages 2361-71

Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ

Abstract

A remarkable overlap was observed between the gadd genes, a group of often coordinately expressed genes that are induced by genotoxic stress and certain other growth arrest signals, and the MyD genes, a set of myeloid differentiation primary response genes. The MyD116 gene was found to be the murine homolog of the hamster gadd34 gene, whereas MyD118 and gadd45 were found to represent two separate but closely related genes. Furthermore, gadd34/MyD116, gadd45, MyD118, and gadd153 encode acidic proteins with very similar and unusual charge characteristics; both this property and a similar pattern of induction are shared with mdm2, whic, like gadd45, has been shown previously to be regulated by the tumor suppressor p53. Expression analysis revealed that they are distinguished from other growth arrest genes in that they are DNA damage inducible and suggest a role for these genes in growth arrest and apoptosis either coupled with or uncoupled from terminal differentiation. Evidence is also presented for coordinate induction in vivo by stress. The use of a short-term transfection assay, in which expression vectors for one or a combination of these gadd/MyD genes were transfected with a selectable marker into several different human tumor cell lines, provided direct evidence for the growth-inhibitory functions of the products of these genes and their ability to synergistically suppress growth. Taken together, these observations indicate that these genes define a novel class of mammalian genes encoding acidic proteins involved in the control of cellular growth.

Related Genes
MyD MyD116 MyD118 gadd gadd153 gadd34 gadd45 mdm2 p53
MeSH Terms
3T3 Cells Amino Acid Sequence Animals Apoptosis/genetics Cell Differentiation Cell Division/genetics Cricetinae Gene Expression Genes, p53 Growth Inhibitors/genetics Humans Mammals/genetics Mice Molecular Sequence Data Proteins/genetics,physiology Sequence Homology, Amino Acid Species Specificity Transcription, Genetic Transfection Tumor Cells, Cultured
Chemicals
Growth Inhibitors Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Zhan Q
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892.
Lord K A
Alamo I
Hollander M C
Carrier F
Ron D
Kohn K W
Hoffman B
Liebermann D A
Fornace A J
References (43)
43 references, click to expand
  1. Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells.
    Mol Cell Biol. 1991 Mar;11(3):1372-81 PMID: 1996099
  2. Analysis of the mammalian gadd45 gene and its response to DNA damage.
    J Biol Chem. 1993 Nov 15;268(32):24385-93 PMID: 8226988
  3. Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc.
    Mol Cell Biol. 1991 May;11(5):2375-81 PMID: 1901940
  4. Neurovirulence factor.
    Nature. 1991 Oct 17;353(6345):609 PMID: 1656275
  5. Cell growth inhibition by prostaglandin A2 results in elevated expression of gadd153 mRNA.
    Exp Cell Res. 1992 Mar;199(1):85-9 PMID: 1735464
  6. Morphological, oncogenic, and karyological characteristics of Syrian hamster embryo cells transformed in vitro by carcinogenic polycyclic hydrocarbons.
    Cancer Res. 1971 Aug;31(8):1118-27 PMID: 5095977
  7. Recombination of parent and daughter strand DNA after UV-irradiation in mammalian cells.
    Nature. 1983 Aug 11-17;304(5926):552-4 PMID: 6877378
  8. Genes specifically expressed at growth arrest of mammalian cells.
    Cell. 1988 Sep 9;54(6):787-93 PMID: 3409319
  9. DNA damage-inducible transcripts in mammalian cells.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8800-4 PMID: 3194391
  10. Regulation of enzyme levels by proteolysis: the role of pest regions.
    Adv Enzyme Regul. 1988;27:135-51 PMID: 2907964
  11. Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents.
    Mol Cell Biol. 1989 Oct;9(10):4196-203 PMID: 2573827
  12. The product of the H19 gene may function as an RNA.
    Mol Cell Biol. 1990 Jan;10(1):28-36 PMID: 1688465
  13. Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene.
    Mol Cell Biol. 1990 Feb;10(2):577-84 PMID: 2300055
  14. An inducible 50-kilodalton NF kappa B-like protein and a constitutive protein both bind the acute-phase response element of the angiotensinogen gene.
    Mol Cell Biol. 1990 Mar;10(3):1023-32 PMID: 2106065
  15. Complexity of the immediate early response of myeloid cells to terminal differentiation and growth arrest includes ICAM-1, Jun-B and histone variants.
    Oncogene. 1990 Mar;5(3):387-96 PMID: 1690380
  16. Regulation of expression of growth arrest-specific genes in mouse fibroblasts.
    Mol Cell Biol. 1990 Apr;10(4):1525-9 PMID: 1690845
  17. Sequence of MyD116 cDNA: a novel myeloid differentiation primary response gene induced by IL6.
    Nucleic Acids Res. 1990 May 11;18(9):2823 PMID: 2339071
  18. Estimation of relative mRNA content by filter hybridization to a polythymidylate probe.
    Biotechniques. 1990 Aug;9(2):174-9 PMID: 2205249
  19. Increased gene expression of Alzheimer disease beta-amyloid precursor protein in senescent cultured fibroblasts.
    Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):16-20 PMID: 1702541
  20. Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C.
    Mol Cell Biol. 1991 Feb;11(2):1009-16 PMID: 1990262
  21. Structure and expression of a gene encoding a putative GTP-binding protein identified by provirus integration in a transgenic mouse strain.
    Mol Cell Biol. 1991 Feb;11(2):886-93 PMID: 1899287
  22. Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines.
    Oncogene. 1991 Jan;6(1):165-7 PMID: 1899477
  23. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription.
    Genes Dev. 1992 Mar;6(3):439-53 PMID: 1547942
  24. The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3266-70 PMID: 1314384
  25. Mammalian stress response: induction of the glucose-regulated protein family.
    Curr Opin Cell Biol. 1992 Apr;4(2):267-73 PMID: 1599691
  26. Amplification of a gene encoding a p53-associated protein in human sarcomas.
    Nature. 1992 Jul 2;358(6381):80-3 PMID: 1614537
  27. Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins.
    Cancer Res. 1992 Jul 1;52(13):3814-7 PMID: 1617653
  28. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation.
    Cell. 1992 Jun 26;69(7):1237-45 PMID: 1535557
  29. Chance and statistical significance in protein and DNA sequence analysis.
    Science. 1992 Jul 3;257(5066):39-49 PMID: 1621093
  30. Isolation, characterization and chromosomal localization of the human GADD153 gene.
    Gene. 1992 Jul 15;116(2):259-67 PMID: 1339368
  31. Wild-type p53 is a cell cycle checkpoint determinant following irradiation.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 PMID: 1323840
  32. p53 function and dysfunction.
    Cell. 1992 Aug 21;70(4):523-6 PMID: 1505019
  33. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus.
    Cell. 1992 Oct 30;71(3):515-26 PMID: 1423610
  34. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia.
    Cell. 1992 Nov 13;71(4):587-97 PMID: 1423616
  35. p53 is required for radiation-induced apoptosis in mouse thymocytes.
    Nature. 1993 Apr 29;362(6423):847-9 PMID: 8479522
  36. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53.
    Nature. 1993 Apr 29;362(6423):857-60 PMID: 8479525
  37. Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis.
    Blood. 1993 May 1;81(9):2257-62 PMID: 8481508
  38. Definition of a consensus binding site for p53.
    Nat Genet. 1992 Apr;1(1):45-9 PMID: 1301998
  39. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents.
    Cancer Res. 1993 May 15;53(10 Suppl):2212-6 PMID: 8485705
  40. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.
    Nature. 1993 Jun 17;363(6430):640-4 PMID: 8510758
  41. Induction of cellular p53 activity by DNA-damaging agents and growth arrest.
    Mol Cell Biol. 1993 Jul;13(7):4242-50 PMID: 8321226
  42. Regulation of the C/EBP-related gene gadd153 by glucose deprivation.
    Mol Cell Biol. 1993 Aug;13(8):4736-44 PMID: 8336711
  43. Dissection of the immediate early response of myeloid leukemia cells to terminal differentiation and growth inhibitory stimuli.
    Cell Growth Differ. 1990 Dec;1(12):637-45 PMID: 2126951
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.4.2361-2371.1994
Published
1994-04-00
Pages
2361-71
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358603
Subset
IM
Databases
GENBANK
L28147, L28177
External Links
PubMed source DOI: 10.1128/mcb.14.4.2361-2371.1994 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2