Home LiteratureArticle Details
PMID: 9271375 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of putative c-Myc-responsive genes: characterization of rcl, a novel growth-related gene.

Molecular and cellular biology ·Vol. 17 ·No. 9 ·1997-09-00 ·Pages 4967-78

Lewis BC, Shim H, Li Q, Wu CS, Lee LA, Maity A, Dang CV

Abstract

The c-Myc protein is a helix-loop-helix leucine zipper oncogenic transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. The biochemical function of c-Myc has been well described, yet the identities of downstream effectors are just beginning to emerge. We describe the identification of a set of c-Myc-responsive genes in the Rat1a fibroblast through the application of cDNA representational difference analysis (RDA) to cDNAs isolated from nonadherent Rat1a and Rat1a-myc cells. In this system, c-Myc overexpression is sufficient to induce the transformed phenotype of anchorage-independent growth. We identified 20 differentially expressed cDNAs, several of which represent novel cDNA sequences. We further characterized one of the novel cDNAs identified in this screen, termed rcl. rcl expression is (i) directly stimulated by c-Myc; (ii) stimulated in the in vivo growth system of regenerating rat liver, as is c-myc; and (iii) elevated in human lymphoid cells that overexpress c-myc. By using an anti-Rcl antibody, immunoblot analysis, and immunofluorescence microscopy, the Rcl protein was found to be a 23-kDa nuclear protein. Ectopic expression of the protein encoded by the rcl cDNA induces anchorage-independent growth in Rat1a fibroblasts, albeit to a diminished extent compared to ectopic c-Myc expression. These data suggest a role for rcl during cellular proliferation and c-Myc-mediated transformation.

MeSH Terms
Amino Acid Sequence Animals COS Cells Cell Adhesion Cell Division/genetics Cell Line Fibroblasts/cytology Flow Cytometry Gene Expression Regulation Humans Mice Molecular Sequence Data N-Glycosyl Hydrolases/physiology Nuclear Proteins/genetics Polymerase Chain Reaction Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc/physiology Rats Ribonucleases/metabolism Sequence Alignment
Chemicals
Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc Ribonucleases DNPH1 protein, human DNPH1 protein, rat N-Glycosyl Hydrolases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lewis B C
Department of Medicine, Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Shim H
Li Q
Wu C S
Lee L A
Maity A
Dang C V
References (58)
58 references, click to expand
  1. Direct role for Myc in transcription initiation mediated by interactions with TFII-I.
    Nature. 1993 Sep 23;365(6444):359-61 PMID: 8377829
  2. The "initiator" as a transcription control element.
    Cell. 1989 Apr 7;57(1):103-13 PMID: 2467742
  3. Regulation of human ornithine decarboxylase expression by the c-Myc.Max protein complex.
    J Biol Chem. 1993 Dec 25;268(36):27277-85 PMID: 8262968
  4. c-Myc induces the expression and activity of ornithine decarboxylase.
    Cell Growth Differ. 1993 Nov;4(11):879-83 PMID: 8297793
  5. An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc.
    Mol Cell Biol. 1994 Jun;14(6):3853-62 PMID: 8196628
  6. Repression of cyclin D1: a novel function of MYC.
    Mol Cell Biol. 1994 Jun;14(6):4032-43 PMID: 8196642
  7. c-Myc binds to 5' flanking sequence motifs of the dihydrofolate reductase gene in cellular extracts: role in proliferation.
    Nucleic Acids Res. 1994 Jun 25;22(12):2264-73 PMID: 8036154
  8. Participation of cyclin A in Myc-induced apoptosis.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6875-9 PMID: 8041712
  9. Cloning of mid-G1 serum response genes and identification of a subset regulated by conditional myc expression.
    Mol Biol Cell. 1994 Mar;5(3):375-88 PMID: 8049528
  10. Effects of c-myc expression on cell cycle progression.
    Mol Cell Biol. 1994 Sep;14(9):5748-55 PMID: 8065309
  11. c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II.
    EMBO J. 1994 Sep 1;13(17):4070-9 PMID: 8076602
  12. The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase.
    Mol Cell Biol. 1994 Dec;14(12):8282-91 PMID: 7969164
  13. Tissue and age specific expression of the myc proto-oncogene family throughout the life span of the C57BL/6J mouse strain.
    Oncogene. 1989 Apr;4(4):465-71 PMID: 2470008
  14. Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells.
    Nature. 1989 Jul 6;340(6228):66-8 PMID: 2662015
  15. Nuclear and nucleolar targeting sequences of c-erb-A, c-myb, N-myc, p53, HSP70, and HIV tat proteins.
    J Biol Chem. 1989 Oct 25;264(30):18019-23 PMID: 2553699
  16. The MYC protein activates transcription of the alpha-prothymosin gene.
    EMBO J. 1991 Jan;10(1):133-41 PMID: 1989881
  17. Transcriptional suppression of cellular gene expression by c-Myc.
    Mol Cell Biol. 1991 Apr;11(4):2291-5 PMID: 2005911
  18. Myc meets its Max.
    Cell. 1991 May 31;65(5):715-6 PMID: 2040011
  19. G1/S control of anchorage-independent growth in the fibroblast cell cycle.
    J Cell Biol. 1991 Dec;115(5):1419-25 PMID: 1955482
  20. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF.
    Nature. 1991 Nov 21;354(6350):245-8 PMID: 1961251
  21. c-myc oncoprotein function.
    Biochim Biophys Acta. 1991 Dec 10;1072(2-3):103-13 PMID: 1751543
  22. Induction of apoptosis in fibroblasts by c-myc protein.
    Cell. 1992 Apr 3;69(1):119-28 PMID: 1555236
  23. A new bind for Myc.
    Trends Genet. 1992 Mar;8(3):91-6 PMID: 1579994
  24. Myc and Max function as a nucleoprotein complex.
    Curr Opin Genet Dev. 1992 Apr;2(2):227-35 PMID: 1638116
  25. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.
    Science. 1992 Aug 14;257(5072):967-71 PMID: 1354393
  26. Function of the c-Myc oncoprotein.
    FASEB J. 1992 Sep;6(12):3065-72 PMID: 1521738
  27. Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes.
    Oncogene. 1992 Dec;7(12):2399-405 PMID: 1461648
  28. c-myc transactivates the ornithine decarboxylase gene.
    Curr Top Microbiol Immunol. 1992;182:445-52 PMID: 1490383
  29. Cloning the differences between two complex genomes.
    Science. 1993 Feb 12;259(5097):946-51 PMID: 8438152
  30. Differential modulation of cyclin gene expression by MYC.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3685-9 PMID: 8386381
  31. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation.
    Nature. 1993 May 6;363(6424):45-51 PMID: 8479536
  32. A cell cycle and mutational analysis of anchorage-independent growth: cell adhesion and TGF-beta 1 control G1/S transit specifically.
    J Cell Biol. 1993 Jul;122(2):461-71 PMID: 8320267
  33. Cell cycle regulation of the c-Myc transcriptional activation domain.
    Mol Cell Biol. 1993 Jul;13(7):4125-36 PMID: 8321217
  34. Cdc25 cell-cycle phosphatase as a target of c-myc.
    Nature. 1996 Aug 8;382(6591):511-7 PMID: 8700224
  35. An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.
    Mol Cell Biol. 1996 Sep;16(9):4754-64 PMID: 8756633
  36. Transformation by the Bmi-1 oncoprotein correlates with its subnuclear localization but not its transcriptional suppression activity.
    Mol Cell Biol. 1996 Oct;16(10):5527-35 PMID: 8816465
  37. Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.
    EMBO J. 1996 Aug 15;15(16):4344-57 PMID: 8861962
  38. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth.
    Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6658-63 PMID: 9192621
  39. The ornithine decarboxylase gene is a transcriptional target of c-Myc.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804-8 PMID: 8356088
  40. The induction of differentiation in teratocarcinoma stem cells by retinoic acid.
    Cell. 1978 Oct;15(2):393-403 PMID: 214238
  41. Translocations among antibody genes in human cancer.
    Science. 1983 Nov 18;222(4625):765-71 PMID: 6356357
  42. Differential expression of myc family genes during murine development.
    Nature. 1986 Feb 27-Mar 5;319(6056):780-3 PMID: 2419762
  43. Identification of the mouse low-salt-eluting single-stranded DNA-binding protein as a mammalian lactate dehydrogenase-A isoenzyme.
    Biochem J. 1986 Feb 1;233(3):913-6 PMID: 3707535
  44. Decreased c-myc expression is an early event in retinoic acid-induced differentiation of F9 teratocarcinoma cells.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5539-43 PMID: 3526333
  45. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  46. Lactate dehydrogenase and glyceraldehyde-phosphate dehydrogenase are single-stranded DNA-binding proteins that affect the DNA-polymerase-alpha-primase complex.
    Eur J Biochem. 1986 Nov 3;160(3):459-67 PMID: 3536507
  47. Pathogenesis of Burkitt lymphoma: expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts.
    Cell. 1987 Apr 24;49(2):161-70 PMID: 3032447
  48. Definition of regions in human c-myc that are involved in transformation and nuclear localization.
    Mol Cell Biol. 1987 May;7(5):1697-709 PMID: 3299053
  49. An improved method for the immunocytochemical detection of bromodeoxyuridine labeled nuclei using flow cytometry.
    Cytometry. 1987 Jul;8(4):372-6 PMID: 3113895
  50. Identifying differences in mRNA expression by representational difference analysis of cDNA.
    Nucleic Acids Res. 1994 Dec 25;22(25):5640-8 PMID: 7838717
  51. An E-box-mediated increase in cad transcription at the G1/S-phase boundary is suppressed by inhibitory c-Myc mutants.
    Mol Cell Biol. 1995 May;15(5):2527-35 PMID: 7739536
  52. Cyclin A links c-Myc to adhesion-independent cell proliferation.
    J Biol Chem. 1995 Jul 7;270(27):15923-5 PMID: 7608142
  53. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain.
    Mol Cell Biol. 1995 Aug;15(8):4031-42 PMID: 7623799
  54. Identification of target genes for the Ewing's sarcoma EWS/FLI fusion protein by representational difference analysis.
    Mol Cell Biol. 1995 Aug;15(8):4623-30 PMID: 7623854
  55. c-Myc and apoptosis.
    Biochim Biophys Acta. 1995 Jul 28;1242(1):11-28 PMID: 7626652
  56. A link between c-Myc-mediated transcriptional repression and neoplastic transformation.
    J Clin Invest. 1996 Apr 1;97(7):1687-95 PMID: 8601634
  57. Chromosomal approaches to the molecular basis of neoplasia.
    Symp Fundam Cancer Res. 1986;39:17-29 PMID: 3321306
  58. An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence.
    Genes Dev. 1992 Dec;6(12B):2513-23 PMID: 1340466
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.9.4967
Published
1997-09-00
Pages
4967-78
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232348
Subset
IM
Grants
NCI NIH HHS · CA57341 · United States
NIGMS NIH HHS · NIGMS07814 · United States
Databases
GENBANK
AF040105, U82591, U83666
External Links
PubMed source DOI: 10.1128/MCB.17.9.4967 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: [email protected]

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