Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target.
The discovery of the p73 and p63 genes, homologous to p53 tumor suppressor has uncovered a family of transcription factors and widened the scenario of cell cycle control and apoptosis. We have identified a putative p53-responsive element in the human adenosine deaminase (ADA) gene, an important enzyme involved in nucleotide metabolism, the deficit of which causes the inhibition of DNA synthesis and repair. Here, we demonstrate that the ectopic expression of p73 isoforms leads to the ADA gene upregulation, showing for the first time a correlation between p73 and ADA. We found that p73 promotes ADA gene expression following a dNTP unbalance generated by ADA enzyme deficiency and 2'deoxyadenosine accumulation. The abrogation of p73 transcriptional activity by the specific dominant-negative p73DD abolishes ADA induction. By contrast, the ADA gene does not appear to be a functional p53 target in the physiological conditions we tested. On the whole, our results contribute to the emerging picture that p73 could play a different role from p53 in normal growth and development by inducing alternative target genes, which are not shared by p53.
Tullo
Apollonia
A
Istituto di Tecnologie Biomediche, Sezione di Bari di Bioinformatica e Genomica CNR, Via Amendola, 165/A Bari 70126, Italy. tullo@area.ba.cnr.it
Mastropasqua
Giuseppe
G
Bourdon
Jean Christophe
JC
Centonze
Paola
P
Gostissa
Monica
M
Costanzo
Antonio
A
Levrero
Massimo
M
Del Sal
Giannino
G
Saccone
Cecilia
C
Sbisà
Elisabetta
E
D000243:Adenosine Deaminase / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D003839:Deoxyadenosines / Q000378:metabolism / Q000494:pharmacology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D015649:Pentostatin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D003839:Deoxyadenosines; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D015649:Pentostatin; D000243:Adenosine Deaminase