p53-independent upregulation of p21WAF1 in NIH 3T3 cells malignantly transformed by mot-2.
Mot-2 protein is shown to interact with p53 and inhibit its transcriptional activation function. Mot-2 overexpressing stable clones of NIH 3T3 cells were malignantly transformed, however, they had a high level of expression of a p53 downstream gene, p21WAF1. The present study was undertaken to elucidate possible molecular mechanism(s) of such upregulation. An increased level of p21WAF1 expression was detected in stable transfectants although an exogenous reporter gene driven by p21WAF1 promoter exhibited lower activity in these cells suggesting that some post-transcriptional mechanism contributes to upregulation. Western analyses of transient and stable clones revealed that upregulation of p21WAF1 in stable NIH 3T3/mot-2 cells may be mediated by cyclin D1 and cdk-2.
Takano
S
S
National Institute of Bioscience and Human-Technology, AIST, Tsukuba, Ibaraki, Japan.
Wadhwa
R
R
Mitsui
Y
Y
Kaul
S C
SC
D016475:3T3 Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology; D002461:Cell Line, Transformed / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018840:HSP70 Heat-Shock Proteins; C115087:Hspa9-ps1 protein, mouse; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases