Functional replacement of the intracellular region of the Notch1 receptor by Epstein-Barr virus nuclear antigen 2.
The intracellular region (RAMIC) of the mouse Notch1 receptor interacts with RBP-J/CBF-1, which binds to the DNA sequence CGTGGGAA and suppresses differentiation by transcriptional activation of genes regulated by RBP-J. Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for immortalization of human B cells by the virus. EBNA2 is a pleiotropic activator of viral and cellular genes and is targeted to DNA at least in part by interacting with RBP-J. We found that EBNA2 and the Notch1 RAMIC compete for binding to RBP-J, indicating that their interaction sites on RBP-J overlap at least partially. EBNA2 and Notch1 RAMIC transactivated the same set of viral and host promoters, i.e., the EBNA2 response element of the Epstein-Barr virus TP1 and the HES-1 promoter. Furthermore, EBNA2 functionally replaced the Notch1 RAMIC by suppressing differentiation of C2C12 myoblast progenitor cells.
Sakai
T
T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan.
Taniguchi
Y
Y
Tamura
K
K
Minoguchi
S
S
Fukuhara
T
T
Strobl
L J
LJ
Zimber-Strobl
U
U
Bornkamm
G W
GW
Honjo
T
T
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000502:physiology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins / Q000502:physiology*; D009132:Muscles / Q000166:cytology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors