p73 is a p53-independent, Sp1-dependent repressor of cyclin B1 transcription.
The p53 protein family, comprised of p53, p63, and p73, has an important role in controlling cell growth and differentiation. We have previously reported that p53 prevents G(2)/M transition by decreasing intracellular levels of both cyclin B1 mRNA and protein, and attenuating the activity of the cyclin B1 promoter. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that a cyclin B1-dependent G(2) checkpoint has a role in preventing neoplastic transformation. There is high sequence similarity between p73 and p53, suggesting that the two may have similar ability to repress transcription. In this report, we find that expression of p73alpha and p73beta isoforms can decrease the levels of cyclin B1 mRNA and attenuate expression from the cyclin B1 promoter. This attenuation occurs in both p53-deficient and p53-containing cell lines and cannot be inhibited by a p53 variant deficient in repressing cyclin B1 promoter activity. p73-mediated attenuation of the cyclin B1 promoter is dependent on the presence of functional Sp1-binding sites and is independent of the NF-Y-binding sites. This suggests that p73 mediates transcriptional repression through the Sp1 transcription factor.
Innocente
Steven A
SA
Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada.
Lee
Jonathan M
JM
D002460:Cell Line; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C090698:SP1 antigen; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins