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PMID: 8421051 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis.

The Journal of cell biology ·Vol. 120 ·No. 2 ·1993-01-00 ·Pages 313-23

Ren M, Drivas G, D'Eustachio P, Rush MG

Abstract

Ran/TC4, first identified as a well-conserved gene distantly related to H-RAS, encodes a protein which has recently been shown in yeast and mammalian systems to interact with RCC1, a protein whose function is required for the normal coupling of the completion of DNA synthesis and the initiation of mitosis. Here, we present data indicating that the nuclear localization of Ran/TC4 requires the presence of RCC1. Transient expression of a Ran/TC4 protein with mutations expected to perturb GTP hydrolysis disrupts host cell DNA synthesis. These results suggest that Ran/TC4 and RCC1 are components of a GTPase switch that monitors the progress of DNA synthesis and couples the completion of DNA synthesis to the onset of mitosis.

Related Genes
MeSH Terms
Amino Acid Sequence Animals Cell Line Cell Nucleus/metabolism,ultrastructure Chromatin/physiology,ultrastructure Chromosomes/physiology,ultrastructure Cricetinae DNA/biosynthesis DNA Replication Fluorescent Antibody Technique GTP Phosphohydrolases/metabolism GTP-Binding Proteins/genetics,metabolism Humans Kidney Mice Mitosis Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/genetics,metabolism Oligodeoxyribonucleotides Sequence Homology, Amino Acid Subcellular Fractions/metabolism Transfection ran GTP-Binding Protein
Chemicals
Chromatin Nuclear Proteins Oligodeoxyribonucleotides DNA GTP Phosphohydrolases GTP-Binding Proteins ran GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ren M
Department of Cell Biology, New York University Medical Center, NY 10016.
Drivas G
D'Eustachio P
Rush M G
References (32)
32 references, click to expand
  1. 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
  2. Premature of chromosome condensation in a ts DNA- mutant of BHK cells.
    Cell. 1978 Oct;15(2):475-83 PMID: 719750
  3. Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus.
    Cell. 1990 Jun 1;61(5):811-23 PMID: 2160859
  4. Vectors used for expression in mammalian cells.
    Methods Enzymol. 1990;185:487-511 PMID: 2381327
  5. Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
    J Cell Biol. 1990 Sep;111(3):807-16 PMID: 2391365
  6. The GTPase superfamily: a conserved switch for diverse cell functions.
    Nature. 1990 Nov 8;348(6297):125-32 PMID: 2122258
  7. A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8617-21 PMID: 2236072
  8. Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol-linked membrane protein.
    J Biol Chem. 1990 Dec 5;265(34):20784-9 PMID: 2249987
  9. The GTPase superfamily: conserved structure and molecular mechanism.
    Nature. 1991 Jan 10;349(6305):117-27 PMID: 1898771
  10. Identification and characterization of a human homolog of the Schizosaccharomyces pombe ras-like gene YPT-3.
    Oncogene. 1991 Jan;6(1):3-9 PMID: 1704119
  11. Protein kinases and protooncogenes: biochemical regulators of the eukaryotic cell cycle.
    Biochemistry. 1991 Mar 5;30(9):2293-302 PMID: 2001361
  12. Nuclear protein localization.
    Biochim Biophys Acta. 1991 Mar 7;1071(1):83-101 PMID: 2004116
  13. Loss of RCC1, a nuclear DNA-binding protein, uncouples the completion of DNA replication from the activation of cdc2 protein kinase and mitosis.
    EMBO J. 1991 Jun;10(6):1555-64 PMID: 1851087
  14. Evolutionary grouping of the RAS-protein family.
    Biochem Biophys Res Commun. 1991 May 15;176(3):1130-5 PMID: 2039498
  15. Coupling M phase and S phase: controls maintaining the dependence of mitosis on chromosome replication.
    Cell. 1991 Jun 14;65(6):921-3 PMID: 2044152
  16. Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase.
    Cell. 1991 Jul 26;66(2):347-60 PMID: 1855255
  17. Structure and function of signal-transducing GTP-binding proteins.
    Annu Rev Biochem. 1991;60:349-400 PMID: 1909108
  18. Selective extraction of polyoma DNA from infected mouse cell cultures.
    J Mol Biol. 1967 Jun 14;26(2):365-9 PMID: 4291934
  19. DNA-binding domain of RCC1 protein is not essential for coupling mitosis with DNA replication.
    J Cell Sci. 1992 Jul;102 ( Pt 3):393-400 PMID: 1506422
  20. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system.
    Cell. 1981 Dec;27(2 Pt 1):279-88 PMID: 6277501
  21. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection.
    Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81 PMID: 6294651
  22. ras genes.
    Annu Rev Biochem. 1987;56:779-827 PMID: 3304147
  23. The RCC1 protein, a regulator for the onset of chromosome condensation locates in the nucleus and binds to DNA.
    J Cell Biol. 1989 Oct;109(4 Pt 1):1389-97 PMID: 2677018
  24. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1.
    Nature. 1991 Nov 7;354(6348):80-2 PMID: 1944575
  25. Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide.
    Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10830-4 PMID: 1961752
  26. Isoprenoid modification and plasma membrane association: critical factors for ras oncogenicity.
    Cancer Cells. 1991 Sep;3(9):331-40 PMID: 1751286
  27. Transport of microinjected proteins into peroxisomes of mammalian cells: inability of Zellweger cell lines to import proteins with the SKL tripeptide peroxisomal targeting signal.
    Mol Cell Biol. 1992 Feb;12(2):531-41 PMID: 1732729
  28. The cdc25 M-phase inducer: an unconventional protein phosphatase.
    Cell. 1992 Feb 7;68(3):407-10 PMID: 1310893
  29. Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2.
    Cell. 1992 Feb 21;68(4):787-97 PMID: 1531451
  30. The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate.
    Mol Cell Biol. 1992 May;12(5):2186-92 PMID: 1569948
  31. RCC1, a regulator of mitosis, is essential for DNA replication.
    Mol Cell Biol. 1992 Aug;12(8):3337-45 PMID: 1630449
  32. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line.
    Mol Cell Biol. 1990 Apr;10(4):1793-8 PMID: 2108320
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1993-01-00
Pages
313-23
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119524
Subset
IM
Grants
NIGMS NIH HHS · GM07827 · United States
NCRR NIH HHS · RR083990 · United States
Databases
GENBANK
M31469
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