Phosphatidylinositol 3-kinase/Akt pathway targets acetylation of Smad3 through Smad3/CREB-binding protein interaction: contribution to transforming growth factor beta1-induced Epstein-Barr virus reactivation.
Epstein-Barr virus, a ubiquitous human herpesvirus, is associated with the development of carcinomas and lymphomas. We previously showed that transforming growth factor beta1 (TGF-beta1) mediated the virus to enter the lytic cycle, which is triggered by expression of Z Epstein-Barr virus replication activator (ZEBRA), through the ERK 1/2 MAPK signaling pathway. We report here that Akt, activated downstream from ERK 1/2, was required for TGF-beta1-induced ZEBRA expression and enabled Smad3, a mediator of TGF-beta1 signaling, to be acetylated by direct interaction with the co-activator CREB-binding protein and then to regulate TGF-beta1-induced ZEBRA expression.
Oussaief
Lassad
L
UMR542 INSERM-Université Paris 11, Hôpital Paul Brousse, 94807 Villejuif Cedex, France.
Hippocrate
Aurélie
A
Ramirez
Vanessa
V
Rampanou
Aurore
A
Zhang
Wei
W
Meyers
David
D
Cole
Philip
P
Khelifa
Ridha
R
Joab
Irène
I
D000107:Acetylation / Q000187:drug effects; D050882:CREB-Binding Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins / Q000378:metabolism*; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology*
C063676:BZLF1 protein, Herpesvirus 4, Human; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D014764:Viral Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3