Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A.
Transforming viral proteins such as E1A force cells through the restriction point of the cell cycle into S phase by forming complexes with two cellular proteins: the retinoblastoma protein (Rb), a transcriptional co-repressor, and CBP/p300, a transcriptional co-activator. These two proteins locally influence chromatin structure: Rb recruits a histone deacetylase, whereas CBP is a histone acetyltransferase. Progression through the restriction point is triggered by phosphorylation of Rb, leading to disruption of Rb-associated repressive complexes and allowing the activation of S-phase genes. Here we show that CBP, like Rb, is controlled by phosphorylation at the G1/S boundary, increasing its histone acetyltransferase activity. This enzymatic activation is mimicked by E1A.
Ait-Si-Ali
S
S
Laboratoire Oncogénèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Villejuif, France.
Ramirez
S
S
Barre
F X
FX
Dkhissi
F
F
Magnaghi-Jaulin
L
L
Girault
J A
JA
Robin
P
P
Knibiehler
M
M
Pritchard
L L
LL
Ducommun
B
B
Trouche
D
D
Harel-Bellan
A
A
D016475:3T3 Cells; D000123:Acetyltransferases / Q000378:metabolism*; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D042846:CDC2-CDC28 Kinases; D050882:CREB-Binding Protein; D002453:Cell Cycle; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D016193:G1 Phase; D051548:Histone Acetyltransferases; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D017500:Adenovirus E1A Proteins; D019927:Cyclin E; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051548:Histone Acetyltransferases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases