In good times and bad: p73 in cancer.
It is widely accepted in cancer biology that p53 has a tumor suppressive activity, which is lost during tumorigenesis most frequently by mutations in the p53 gene. The discovery of p73 as the first homologue of p53 raised immediate expectations about p53-like tumor suppressor activities. Although tumors show changes in the expression level of p73 and differences in the expression pattern of p73 isoforms, mutations are not commonly observed making it difficult to infer p73's role in tumorigenesis. An experimental model of human cell transformation closely mimics the expression changes observed in cancer patients and provides novel insights into the regulation and function of p73 in the various steps on the road to malignant transformation. p53-like isoforms of p73 (TAp73) are upregulated early during the transformation process in response to RB pathway alterations and block progression to the fully transformed state. Antagonists of TAp73 such as the dominant-negative p73 protein DeltaNp73 overcome this block and pave the way to full transformation. Here we review these findings in the context of patient data and recent advances on molecular aspects of p73 function and discuss the implications for p73 as a target for cancer therapy.
Oswald
Claudia
C
Department for Hematology, Oncology and Immunology, Institute for Molecular Biology and Tumor Research, Philipps-University Marburg, Marburg, Germany.
Stiewe
Thorsten
T
D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D015689:Oncogene Protein p21(ras)