Nuclear localization is essential for the activity of p53 protein

Oncogene. 1991 Nov;6(11):2055-65.


p53 appears to be a growth regulator, the perturbation of which induces changes in normal cell proliferation. Wild-type p53 protein is thought to function as a growth arrest gene, whereas mutant p53, which accumulates in transformed cells, has been shown to enhance malignant transformation. Both wild-type and mutant p53 migrate into the cell nucleus by means of identical nuclear localization signals (NLS) inherent in their primary sequences. Results presented here show that the suppressive activity of wild-type p53 measured as the reduction of transformation of primary rat fibroblasts induced by co-transfection with ras and either E1A or mutant p53, as well as the transformation enhancement of mutant p53 estimated by cooperation with ras in transformation of primary rat fibroblasts, is dependent upon nuclear localization signals in p53 protein. While transfection of unmodified wild-type p53 significantly reduces the number of rat embryonic fibroblast-transformed foci induced by E1A and ras or mutant p53 and ras, the wild-type p53 protein without NLS has completely lost this suppressive activity. Partially defective NLS wild-type p53, with a reduced nuclear accumulation ability, still exhibits some suppressive activity. In addition, we found that plasmids coding for intact mutant p53 protein efficiently cooperate with the ras oncogene, whereas the corresponding plasmids without NLS are totally inert. On this basis we conclude that nuclear localization of both wild-type and mutant p53 is a fundamental feature for manifesting the activities of these proteins. Both the suppressor activity mediated by the wild-type p53 and enhancement of transformation mediated by the mutant p53 require nuclear localization of the proteins to function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD*
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • Base Sequence
  • Cell Nucleus / chemistry*
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Chromosome Mapping
  • Epitopes / analysis
  • Fluorescent Antibody Technique
  • Genes, ras / physiology
  • Lectins, C-Type
  • Molecular Sequence Data
  • Mutation
  • Nuclear Localization Signals
  • Nuclear Proteins / physiology
  • Plasmids
  • Precipitin Tests
  • Rats
  • Rats, Inbred F344
  • Transfection
  • Transformation, Genetic
  • Tumor Suppressor Protein p53 / physiology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Epitopes
  • Lectins, C-Type
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Tumor Suppressor Protein p53