Nucleophosmin, HDM2 and p53: players in UV damage incited nucleolar stress response.
p53 tumor suppressor protein acts as a critical monitor preventing survival of cells with irreparable genetic damage. Its levels are tightly controlled by its negative regulator HDM2, and are allowed to rise only during cellular stress. In our recent paper (Kurki, et al. Cancer Cell 2004; 5:465-75) we identify a novel mechanism leading to p53 stabilization following UV damage of the cells. This involves UV damage provoked nucleoplasmic relocalization of a nucleolar protein, nucleophosmin (NPM, B23) and its rapid and transient interactions with both p53 and HDM2. We discuss here implications of recent findings that several p53 pathway proteins interact with NPM and find that its participation in cellular damage responses is limited to transcriptional stress but absent in direct ds DNA breaks. These findings suggest divergence in the routes provoking p53 stability and implicate the nucleolus as a central site participating in transcriptional stress responses.
Kurki
Sari
S
Haartman Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Peltonen
Karita
K
Laiho
Marikki
M
D002467:Cell Nucleus / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D000090243:Nucleophosmin; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2