UMMS Affiliation

Department of Cell Biology; Department of Cancer Biology

Publication Date


Document Type



Animals; *Cell Polarity; Cell Proliferation; Cell Transformation, Neoplastic; Chromosomes, Mammalian; Embryo, Mammalian; Fibroblasts; Mice; *Mitosis; Mitotic Spindle Apparatus; Neoplasms; Ploidies; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53


Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



Mol Cell Biol. 2008 Feb;28(4):1265-73. Epub 2007 Nov 26. Link to article on publisher's site

Journal/Book/Conference Title

Molecular and cellular biology

Related Resources

Link to Article in PubMed

PubMed ID