Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

A novel p53-inducible gene coding for a microtubule-localized protein with G2-phase-specific expression.

Author information

Affiliations

  • 1. Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.
      Authors
    • Utrera R 1
    (1 author)

ORCIDs linked to this article

The EMBO Journal, 01 Sep 1998, 17(17):5015-5025
https://doi.org/10.1093/emboj/17.17.5015 PMID: 9724637 PMCID: PMC1170829

Free full text in Europe PMC

Abstract 

Wild-type (wt) p53 can act as a sequence-specific transcriptional activator and it is believed that p53 elicits at least part of its biological effects by regulating the expression of specific target genes. By using a differential subtractive hybridization approach in a murine cell line stably transfected with a temperature-sensitive p53 mutant (Val135), we isolated a set of genes markedly induced by wt p53. One of them, provisionally named B99, was further characterized; its transcriptional induction was dependent on wt p53 function and the corresponding protein product was shown to accumulate after DNA damage in different cell types. Immunofluorescence analysis located the B99 protein to the microtubule network. Flow cytometry revealed that upon activation of p53 function the endogenous B99 protein was selectively induced in the G2 fraction of the cell population. When B99 was ectopically expressed in p53-null murine fibroblasts, B99-transfected cells displayed an increased fraction with a 4N DNA content, indicative of interference with G2 phase progression. Taken together these data suggest that B99 might play a role in mediating specific biological activities of wt p53 during the G2 phase.

Free full text 

Logo of embojLink to Publisher's site
EMBO J. 1998 Sep 1; 17(17): 5015–5025.
PMCID: PMC1170829
PMID: 9724637

A novel p53-inducible gene coding for a microtubule-localized protein with G2-phase-specific expression.

R Utrera, L Collavin, D Lazarević, D Delia, and C Schneider
Author information Copyright and License information Disclaimer

Abstract

Wild-type (wt) p53 can act as a sequence-specific transcriptional activator and it is believed that p53 elicits at least part of its biological effects by regulating the expression of specific target genes. By using a differential subtractive hybridization approach in a murine cell line stably transfected with a temperature-sensitive p53 mutant (Val135), we isolated a set of genes markedly induced by wt p53. One of them, provisionally named B99, was further characterized; its transcriptional induction was dependent on wt p53 function and the corresponding protein product was shown to accumulate after DNA damage in different cell types. Immunofluorescence analysis located the B99 protein to the microtubule network. Flow cytometry revealed that upon activation of p53 function the endogenous B99 protein was selectively induced in the G2 fraction of the cell population. When B99 was ectopically expressed in p53-null murine fibroblasts, B99-transfected cells displayed an increased fraction with a 4N DNA content, indicative of interference with G2 phase progression. Taken together these data suggest that B99 might play a role in mediating specific biological activities of wt p53 during the G2 phase.

Full Text

The Full Text of this article is available as a PDF (746K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agarwal ML, Agarwal A, Taylor WR, Stark GR. p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8493–8497. [Europe PMC free article] [Abstract] [Google Scholar]
  • Andreassen PR, Margolis RL. Microtubule dependency of p34cdc2 inactivation and mitotic exit in mammalian cells. J Cell Biol. 1994 Nov;127(3):789–802. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bates S, Vousden KH. p53 in signaling checkpoint arrest or apoptosis. Curr Opin Genet Dev. 1996 Feb;6(1):12–18. [Abstract] [Google Scholar]
  • Brown CR, Doxsey SJ, White E, Welch WJ. Both viral (adenovirus E1B) and cellular (hsp 70, p53) components interact with centrosomes. J Cell Physiol. 1994 Jul;160(1):47–60. [Abstract] [Google Scholar]
  • Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995 Oct 12;377(6549):552–557. [Abstract] [Google Scholar]
  • Chomczynski P. One-hour downward alkaline capillary transfer for blotting of DNA and RNA. Anal Biochem. 1992 Feb 14;201(1):134–139. [Abstract] [Google Scholar]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [Abstract] [Google Scholar]
  • Cross SM, Sanchez CA, Morgan CA, Schimke MK, Ramel S, Idzerda RL, Raskind WH, Reid BJ. A p53-dependent mouse spindle checkpoint. Science. 1995 Mar 3;267(5202):1353–1356. [Abstract] [Google Scholar]
  • Del Sal G, Ruaro EM, Utrera R, Cole CN, Levine AJ, Schneider C. Gas1-induced growth suppression requires a transactivation-independent p53 function. Mol Cell Biol. 1995 Dec;15(12):7152–7160. [Europe PMC free article] [Abstract] [Google Scholar]
  • Del Sal G, Murphy M, Ruaro E, Lazarevic D, Levine AJ, Schneider C. Cyclin D1 and p21/waf1 are both involved in p53 growth suppression. Oncogene. 1996 Jan 4;12(1):177–185. [Abstract] [Google Scholar]
  • Delia D, Goi K, Mizutani S, Yamada T, Aiello A, Fontanella E, Lamorte G, Iwata S, Ishioka C, Krajewski S, et al. Dissociation between cell cycle arrest and apoptosis can occur in Li-Fraumeni cells heterozygous for p53 gene mutations. Oncogene. 1997 May 8;14(18):2137–2147. [Abstract] [Google Scholar]
  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell. 1995 Aug 25;82(4):675–684. [Abstract] [Google Scholar]
  • el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B. Definition of a consensus binding site for p53. Nat Genet. 1992 Apr;1(1):45–49. [Abstract] [Google Scholar]
  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. [Abstract] [Google Scholar]
  • Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ. 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):531–539. [Europe PMC free article] [Abstract] [Google Scholar]
  • Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal centrosome amplification in the absence of p53. Science. 1996 Mar 22;271(5256):1744–1747. [Abstract] [Google Scholar]
  • Furnari B, Rhind N, Russell P. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science. 1997 Sep 5;277(5331):1495–1497. [Abstract] [Google Scholar]
  • Hansen R, Oren M. p53; from inductive signal to cellular effect. Curr Opin Genet Dev. 1997 Feb;7(1):46–51. [Abstract] [Google Scholar]
  • Harvey DM, Levine AJ. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev. 1991 Dec;5(12B):2375–2385. [Abstract] [Google Scholar]
  • Hecker D, Page G, Lohrum M, Weiland S, Scheidtmann KH. Complex regulation of the DNA-binding activity of p53 by phosphorylation: differential effects of individual phosphorylation sites on the interaction with different binding motifs. Oncogene. 1996 Mar 7;12(5):953–961. [Abstract] [Google Scholar]
  • Hermeking H, Eick D. Mediation of c-Myc-induced apoptosis by p53. Science. 1994 Sep 30;265(5181):2091–2093. [Abstract] [Google Scholar]
  • Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, Kinzler KW, Vogelstein B. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell. 1997 Dec;1(1):3–11. [Abstract] [Google Scholar]
  • Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. [Abstract] [Google Scholar]
  • Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev. 1996 May 1;10(9):1054–1072. [Abstract] [Google Scholar]
  • Lanni JS, Jacks T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol Cell Biol. 1998 Feb;18(2):1055–1064. [Europe PMC free article] [Abstract] [Google Scholar]
  • Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997 Feb 7;88(3):323–331. [Abstract] [Google Scholar]
  • Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene. 1994 Aug;9(8):2261–2268. [Abstract] [Google Scholar]
  • Lin J, Chen J, Elenbaas B, Levine AJ. 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):1235–1246. [Abstract] [Google Scholar]
  • Loignon M, Fetni R, Gordon AJ, Drobetsky EA. A p53-independent pathway for induction of p21waf1cip1 and concomitant G1 arrest in UV-irradiated human skin fibroblasts. Cancer Res. 1997 Aug 15;57(16):3390–3394. [Abstract] [Google Scholar]
  • Luckow B, Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. [Europe PMC free article] [Abstract] [Google Scholar]
  • Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev. 1995 Apr 15;9(8):935–944. [Abstract] [Google Scholar]
  • Martinez J, Georgoff I, Martinez J, Levine AJ. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev. 1991 Feb;5(2):151–159. [Abstract] [Google Scholar]
  • Michalovitz D, Halevy O, Oren M. Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell. 1990 Aug 24;62(4):671–680. [Abstract] [Google Scholar]
  • Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D. Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res. 1994 Jul 1;54(13):3391–3395. [Abstract] [Google Scholar]
  • Murphy M, Hinman A, Levine AJ. Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev. 1996 Dec 1;10(23):2971–2980. [Abstract] [Google Scholar]
  • Olmsted JB. Non-motor microtubule-associated proteins. Curr Opin Cell Biol. 1991 Feb;3(1):52–58. [Abstract] [Google Scholar]
  • Ookata K, Hisanaga S, Bulinski JC, Murofushi H, Aizawa H, Itoh TJ, Hotani H, Okumura E, Tachibana K, Kishimoto T. Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. J Cell Biol. 1995 Mar;128(5):849–862. [Europe PMC free article] [Abstract] [Google Scholar]
  • Sabbatini P, Chiou SK, Rao L, White E. Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein. Mol Cell Biol. 1995 Feb;15(2):1060–1070. [Europe PMC free article] [Abstract] [Google Scholar]
  • Stewart N, Hicks GG, Paraskevas F, Mowat M. Evidence for a second cell cycle block at G2/M by p53. Oncogene. 1995 Jan 5;10(1):109–115. [Abstract] [Google Scholar]
  • Waldman T, Lengauer C, Kinzler KW, Vogelstein B. Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. Nature. 1996 Jun 20;381(6584):713–716. [Abstract] [Google Scholar]
  • Wang Y, Prives C. Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases. Nature. 1995 Jul 6;376(6535):88–91. [Abstract] [Google Scholar]
  • Wu X, Levine AJ. p53 and E2F-1 cooperate to mediate apoptosis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602–3606. [Europe PMC free article] [Abstract] [Google Scholar]
  • Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. [Abstract] [Google Scholar]
Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

Full text links 

Read article at publisher's site: https://doi.org/10.1093/emboj/17.17.5015

Read article for free, from open access legal sources, via Unpaywall: http://emboj.embopress.org/content/17/17/5015.full.pdfUnpaywall

Citations & impact 

Impact metrics

64
Citations
Jump to Citations
8
Data citations
Jump to Data

Citations of article over time

Smart citations by scite.ai
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
Explore citation contexts and check if this article has been supported or disputed.
https://scite.ai/reports/10.1093/emboj/17.17.5015

Supporting
Mentioning
Contrasting
2
99
0

Article citations

Go to all (64) article citations

Data 

Data behind the article

This data has been text mined from the article, or deposited into data resources.

BioStudies: supplemental material and supporting data

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.