This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Matijasevic, Z.
Right arrow Articles by Jones, S. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matijasevic, Z.
Right arrow Articles by Jones, S. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2008, p. 1265-1273, Vol. 28, No. 4
0270-7306/08/$08.00+0     doi:10.1128/MCB.01108-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MdmX Promotes Bipolar Mitosis To Suppress Transformation and Tumorigenesis in p53-Deficient Cells and Mice{triangledown} ,{dagger}

Zdenka Matijasevic,{ddagger} Heather A. Steinman,{ddagger} Kathleen Hoover, and Stephen N. Jones*

Departments of Cell Biology and Cancer Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655

Received 21 June 2007/ Returned for modification 31 July 2007/ Accepted 11 November 2007

Mdm2 and MdmX are structurally related p53-binding proteins that function as critical negative regulators of p53 activity in embryonic and adult tissue. The overexpression of Mdm2 or MdmX inhibits p53 tumor suppressor functions in vitro, and the amplification of Mdm2 or MdmX is observed in human cancers retaining wild-type p53. We now demonstrate a surprising role for MdmX in suppressing tumorigenesis that is distinct from its oncogenic ability to inhibit p53. The deletion of MdmX induces multipolar mitotic spindle formation and the loss of chromosomes from hyperploid p53-null cells. This reduction in chromosome number, not observed in p53-null cells with Mdm2 deleted, correlates with increased cell proliferation and the spontaneous transformation of MdmX/p53-null mouse embryonic fibroblasts in vitro and with an increased rate of spontaneous tumorigenesis in MdmX/p53-null mice in vivo. These results indicate that MdmX has a p53-independent role in suppressing oncogenic cell transformation, proliferation, and tumorigenesis by promoting centrosome clustering and bipolar mitosis.

* Corresponding author. Mailing address: Departments of Cell Biology and Cancer Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. Phone: (508) 856-7500. Fax: (508) 856-7501. E-mail: stephen.jones{at}umassmed.edu

{triangledown} Published ahead of print on 26 November 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, February 2008, p. 1265-1273, Vol. 28, No. 4
0270-7306/08/$08.00+0     doi:10.1128/MCB.01108-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, X., Lin, L., Guo, H., Yang, J., Jones, S. N., Jochemsen, A., Lu, X. (2009). Phosphorylation and Degradation of MdmX Is Inhibited by Wip1 Phosphatase in the DNA Damage Response. Cancer Res. 69: 7960-7968 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»