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PMID: 8524283 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gas1-induced growth suppression requires a transactivation-independent p53 function.

Molecular and cellular biology ·Vol. 15 ·No. 12 ·1995-12-00 ·Pages 7152-60

Del Sal G, Ruaro EM, Utrera R, Cole CN, Levine AJ, Schneider C

Abstract

In normal cells, induction of quiescence is accompanied by the increased expression of growth arrest-specific genes (gas). One of them, gas1, is regulated at the transcriptional level and codes for a membrane-associated protein (Gas1) which is down regulated during the G0-to-S phase transition in serum-stimulated cells. Gas1 is not expressed in growing or transformed cells, and when overexpressed in normal fibroblasts, it blocks the G0-to-S phase transition. Moreover, Gas1 blocks cell proliferation in several transformed cells with the exception of simian virus 40- or adenovirus-transformed cell lines. In this paper, we demonstrate that overexpression of Gas1 blocks cell proliferation in a p53-dependent manner and that the N-terminal domain-dependent transactivating function of p53 is dispensable for Gas1-induced growth arrest. These data therefore indicate that the other intrinsic transactivation-independent functions of p53, possibly related to regulation of apoptosis, should be involved in mediating Gas1-induced growth arrest.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Antibodies Base Sequence Blotting, Western Cell Cycle Cell Cycle Proteins Cell Division/physiology Cell Line, Transformed Chloramphenicol O-Acetyltransferase/analysis,biosynthesis DNA Primers GPI-Linked Proteins Gene Expression Regulation Membrane Proteins/biosynthesis,physiology Mice Mice, Inbred BALB C Molecular Sequence Data Peptide Fragments/chemical synthesis,immunology Polymerase Chain Reaction Recombinant Proteins/analysis,biosynthesis Resting Phase, Cell Cycle S Phase Transcription, Genetic Transcriptional Activation Transfection Tumor Suppressor Protein p53/metabolism
Chemicals
Antibodies Cell Cycle Proteins DNA Primers GAS1 protein, human GPI-Linked Proteins Gas1 protein, mouse Membrane Proteins Peptide Fragments Recombinant Proteins Tumor Suppressor Protein p53 Chloramphenicol O-Acetyltransferase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Del Sal G
Laboratorio Nazionale Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.
Ruaro E M
Utrera R
Cole C N
Levine A J
Schneider C
References (42)
42 references, click to expand
  1. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene.
    Cell. 1988 Jul 15;54(2):275-83 PMID: 2839300
  2. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life.
    Mol Cell Biol. 1988 Feb;8(2):531-9 PMID: 2832726
  3. Linker insertion mutants of simian virus 40 large T antigen that show trans-dominant interference with wild-type large T antigen map to multiple sites within the T-antigen gene.
    J Virol. 1989 Nov;63(11):4777-86 PMID: 2552152
  4. Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53.
    Cell. 1990 Aug 24;62(4):671-80 PMID: 2143698
  5. Presence of a potent transcription activating sequence in the p53 protein.
    Science. 1990 Aug 31;249(4972):1046-9 PMID: 2144363
  6. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene.
    Science. 1990 Aug 31;249(4972):1049-51 PMID: 2144364
  7. p53 functions as a cell cycle control protein in osteosarcomas.
    Mol Cell Biol. 1990 Nov;10(11):5772-81 PMID: 2233717
  8. Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein.
    Mol Cell Biol. 1991 Jan;11(1):582-5 PMID: 1986251
  9. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.
    Genes Dev. 1991 Feb;5(2):151-9 PMID: 1995413
  10. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6.
    Nature. 1991 Jul 25;352(6333):345-7 PMID: 1852210
  11. Participation of p53 protein in the cellular response to DNA damage.
    Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 PMID: 1933891
  12. The ability of simian virus 40 large T antigen to immortalize primary mouse embryo fibroblasts cosegregates with its ability to bind to p53.
    J Virol. 1991 Dec;65(12):6872-80 PMID: 1658380
  13. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts.
    Genes Dev. 1991 Dec;5(12B):2375-85 PMID: 1752433
  14. Transformation of a continuous rat embryo fibroblast cell line requires three separate domains of simian virus 40 large T antigen.
    J Virol. 1992 May;66(5):2780-91 PMID: 1313902
  15. Oncogenic forms of p53 inhibit p53-regulated gene expression.
    Science. 1992 May 8;256(5058):827-30 PMID: 1589764
  16. The growth arrest-specific gene, gas1, is involved in growth suppression.
    Cell. 1992 Aug 21;70(4):595-607 PMID: 1505026
  17. 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
  18. Regulation of the specific DNA binding function of p53.
    Cell. 1992 Nov 27;71(5):875-86 PMID: 1423635
  19. Wild-type p53 binds to the TATA-binding protein and represses transcription.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028-32 PMID: 1465435
  20. p53 is required for radiation-induced apoptosis in mouse thymocytes.
    Nature. 1993 Apr 29;362(6423):847-9 PMID: 8479522
  21. Thymocyte apoptosis induced by p53-dependent and independent pathways.
    Nature. 1993 Apr 29;362(6423):849-52 PMID: 8479523
  22. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53.
    Nature. 1993 May 20;363(6426):281-3 PMID: 8387645
  23. The p53-mdm-2 autoregulatory feedback loop.
    Genes Dev. 1993 Jul;7(7A):1126-32 PMID: 8319905
  24. A comparison of the biological activities of wild-type and mutant p53.
    FASEB J. 1993 Jul;7(10):855-65 PMID: 8344485
  25. Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes?
    Cell. 1993 Nov 19;75(4):765-78 PMID: 8242748
  26. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  27. p21 is a universal inhibitor of cyclin kinases.
    Nature. 1993 Dec 16;366(6456):701-4 PMID: 8259214
  28. Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1848-52 PMID: 8127893
  29. Sequence-specific transcriptional activation is essential for growth suppression by p53.
    Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):1998-2002 PMID: 8134338
  30. New lambda and plasmid vectors for expression cloning in mammalian cells.
    Biotechniques. 1994 Jan;16(1):134-8 PMID: 8136127
  31. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.
    Cell. 1994 Mar 25;76(6):1013-23 PMID: 8137420
  32. p53 and E2F-1 cooperate to mediate apoptosis.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602-6 PMID: 8170954
  33. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes.
    Nature. 1994 Jul 21;370(6486):220-3 PMID: 8028670
  34. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.
    Genes Dev. 1994 May 15;8(10):1235-46 PMID: 7926727
  35. Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.
    Genes Dev. 1994 Dec 1;8(23):2817-30 PMID: 7995520
  36. Transcriptional activation by p53 correlates with suppression of growth but not transformation.
    Cell. 1994 Dec 2;79(5):817-27 PMID: 8001119
  37. Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression.
    Mol Cell Biol. 1995 Jan;15(1):227-34 PMID: 7799929
  38. Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein.
    Mol Cell Biol. 1995 Feb;15(2):1060-70 PMID: 7823921
  39. Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A.
    Genes Dev. 1995 Aug 1;9(15):1846-56 PMID: 7649472
  40. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  41. In vitro mutagenesis of a putative DNA binding domain of SV40 large-T.
    Virology. 1984 Nov;139(1):109-37 PMID: 6093377
  42. Genes specifically expressed at growth arrest of mammalian cells.
    Cell. 1988 Sep 9;54(6):787-93 PMID: 3409319
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.12.7152
Published
1995-12-00
Pages
7152-60
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230971
Subset
IM
Grants
NCI NIH HHS · CA 39259 · United States
External Links
PubMed source DOI: 10.1128/MCB.15.12.7152 PMC Full Text View journal details
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