Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer

Nat Med. 1996 Aug;2(8):912-7. doi: 10.1038/nm0896-912.


The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic
  • DNA Primers
  • Disease Progression
  • Female
  • Humans
  • Leukemia / metabolism
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Protein Binding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2
  • RNA / metabolism
  • Transformation, Genetic
  • Tumor Suppressor Protein p53 / metabolism*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology


  • DNA Primers
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • RNA
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2

Associated data

  • GENBANK/U33199
  • GENBANK/U33200
  • GENBANK/U33201
  • GENBANK/U33202
  • GENBANK/U33203