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PMID: 18818521 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

MdmX regulates transformation and chromosomal stability in p53-deficient cells.

Cell cycle (Georgetown, Tex.) ·Vol. 7 ·No. 19 ·2008-10-00 ·Pages 2967-73

Matijasevic Z, Krzywicka-Racka A, Sluder G, Jones SN

Abstract

The cellular homologues Mdm2 and MdmX play critical roles in regulating the activity of the p53 tumor suppressor in damaged and non-damaged cells and during development in mice. Recently, we have utilized genetically defined primary cells and mice to reveal that endogenous levels of MdmX can also suppress multipolar mitosis and transformation in hyperploid p53-deficient cells and tumorigenesis in p53-deficient mice. These MdmX functions are not shared by Mdm2, and are distinct from the well-established ability of MdmX to complex with and inhibit p53 activity. Here we discuss some of the ramifications of MdmX loss in p53-deficient cells and mice, and we explore further the fate of MdmX/p53-double null embryonic fibroblasts undergoing multi-polar cell division using time-lapse video microscopy. We also discuss the relationship between chromosomal loss, cell proliferation, and the tumorigenic potential of p53-deficient cells lacking MdmX.

MeSH Terms
Animals Cell Division Cell Transformation, Neoplastic Centrosome/metabolism Chromosomal Instability/physiology Humans Mice Mitosis Proto-Oncogene Proteins c-mdm2/genetics,metabolism Tumor Suppressor Protein p53/genetics,metabolism
Chemicals
Tumor Suppressor Protein p53 Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Matijasevic Zdenka
Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Krzywicka-Racka Anna
Sluder Greenfield
Jones Stephen N
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Article Info
Journal
Cell cycle (Georgetown, Tex.)
Abbr.
Cell Cycle
ISSN
1551-4005
DOI
10.4161/cc.7.19.6797
Published
2008-10-00
Epub
2008-00-15
Pages
2967-73
Language
English
Region
United States
NLM ID
101137841
PMCID
PMC2716213
Subset
IM
Grants
NCI NIH HHS · R01 CA077735 · United States
NIGMS NIH HHS · R01 GM030758-27 · United States
NCI NIH HHS · R01CA77735 · United States
NCI NIH HHS · R01 CA077735-09 · United States
NIGMS NIH HHS · R01 GM030758 · United States
NIGMS NIH HHS · R01GM30758 · United States
External Links
PubMed source DOI: 10.4161/cc.7.19.6797 PMC Full Text View journal details
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