TY - JOUR
T1 - p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade
AU - Nozaki, Michimasa
AU - Tada, Mitsuhiro
AU - Kashiwazaki, Haruhiko
AU - Hamou, Marie France
AU - Diserens, Annie Claire
AU - Shinohe, Yumiko
AU - Sawamura, Yutaka
AU - Iwasaki, Yoshinobu
AU - de Tribolet, Nicolas
AU - Hegi, Monika E.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - The p53 gene is normally wild type in meningiomas. Since all three members of the p53 gene family recognize the same DNA sequence, tumors containing wild type p53 could decrease transactivation of p53 target genes by mutating either p63 or p73. In meningiomas the most likely target is p73, because loss of heterozygosity of the chromosomal band containing p73 is the commonest genetic lesion in these tumors. To screen p73 for mutations we have developed a functional assay which tests the ability of p73 to activate transcription from a p53-responsive promoter in yeast. The assay correctly identified p73 mutants with mutations equivalent to hotspot mutations in p53, demonstrating that the assay can detect transcriptionally inactive p73. No mutations in p73 were identified in meningiomas. p73 RNA level was higher in more advanced tumors, but there was no correlation between the expression level of p73 and p21, a known p53 target gene. The yeast assay was also used to measure the intrinsic sensitivity of the p73 protein to mutagenesis. Like p53, p73 is exceptionally easy to inactivate as a transcription factor by point mutation. Taken together, these results indicate that p53 and p73 serve very different functions in tumors.
AB - The p53 gene is normally wild type in meningiomas. Since all three members of the p53 gene family recognize the same DNA sequence, tumors containing wild type p53 could decrease transactivation of p53 target genes by mutating either p63 or p73. In meningiomas the most likely target is p73, because loss of heterozygosity of the chromosomal band containing p73 is the commonest genetic lesion in these tumors. To screen p73 for mutations we have developed a functional assay which tests the ability of p73 to activate transcription from a p53-responsive promoter in yeast. The assay correctly identified p73 mutants with mutations equivalent to hotspot mutations in p53, demonstrating that the assay can detect transcriptionally inactive p73. No mutations in p73 were identified in meningiomas. p73 RNA level was higher in more advanced tumors, but there was no correlation between the expression level of p73 and p21, a known p53 target gene. The yeast assay was also used to measure the intrinsic sensitivity of the p73 protein to mutagenesis. Like p53, p73 is exceptionally easy to inactivate as a transcription factor by point mutation. Taken together, these results indicate that p53 and p73 serve very different functions in tumors.
UR - http://www.scopus.com/inward/record.url?scp=0034988443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034988443&partnerID=8YFLogxK
U2 - 10.1111/j.1750-3639.2001.tb00400.x
DO - 10.1111/j.1750-3639.2001.tb00400.x
M3 - Article
C2 - 11414472
AN - SCOPUS:0034988443
VL - 11
SP - 296
EP - 305
JO - Brain Pathology
JF - Brain Pathology
SN - 1015-6305
IS - 3
ER -