Alterations in expression of E2F-1 and E2F-responsive genes by RB, p53 and p21(Sdi1/WAF1/Cip1) expression.
RB, p53 and p21(Sdi1/WAF1/Cip1) interact in the induction of G1 arrest. We established osteosarcoma cell lines in which a tetracycline-regulatable promoter controls the induction of RB, p53 and p21. By using these cell lines, we investigated whether RB, p53 or p21 regulates, in the same manner or differently, expression and function of E2F-1 and its responsive genes. E2F-1 gene products and transcripts of the E2F-responsive genes decreased in response to RB. Similar changes occurred to p53 and p21 when RB is present. However, in the absence of RB, some of the E2F-responsive genes decreased in response to p53 but not to p21. Thus, RB is a critical component for regulating the E2F-responsive genes, while p53 alone affects only a subset of these genes.
Ookawa
K
K
2nd Department of Biochemistry, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki, Aomori 036-8562, Japan. kookawa@cc.hirosaki-u.ac.jp
Tsuchida
S
S
Kohno
T
T
Yokota
J
J
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D016160:Retinoblastoma Protein / Q000378:metabolism* / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology
C493956:CDKN1A protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53