CBF-1 (RBP-J kappa) binds to the PTEN promoter and regulates PTEN gene expression.
The PTEN gene regulates multiple signaling pathways that influence cell proliferation, survival and differentiation. Loss of PTEN expression is closely linked with oncogenesis. Little is known regarding regulation of PTEN gene expression. The PTEN promoter region has been reported and is regulated in part by p53. In a previous study, we found that Notch-1 signaling resulted in increased PTEN protein expression. Herein, we tested the hypothesis that the PTEN gene is a direct target of Notch-1 signal transduction, through binding of the Notch-activated transcription factor CBF-1 to the PTEN minimal promoter. 293 cells expressing constitutively active Notch-1 exhibited increased PTEN gene expression and promoter transactivation. Overexpression of CBF-1 in 293 cells resulted in decreased PTEN gene expression. Mobility shift assays and supershift assays demonstrated that CBF-1 binds to the PTEN minimal promoter. These data indicate that the Notch-1 receptor pathway is a key regulator of PTEN gene transcription.
Whelan
Jarrett T
JT
Department of Microbiology and Immunology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Forbes
Siiri L
SL
Bertrand
Fred E
FE
D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics
D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497570:RBPJ protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human