Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3T3 Cells
-
Acetyltransferases / metabolism*
-
Adenovirus E1A Proteins / metabolism*
-
Animals
-
CDC2-CDC28 Kinases*
-
CREB-Binding Protein
-
Cell Cycle*
-
Cyclin E / metabolism*
-
Cyclin-Dependent Kinase 2
-
Cyclin-Dependent Kinases / metabolism*
-
Enzyme Activation
-
G1 Phase
-
Histone Acetyltransferases
-
Mice
-
Nuclear Proteins / metabolism*
-
Oncogene Proteins / metabolism*
-
Phosphorylation
-
Protein Serine-Threonine Kinases / metabolism*
-
S Phase
-
Saccharomyces cerevisiae Proteins*
-
Trans-Activators / metabolism*
-
Transcriptional Activation
-
Transfection
Substances
-
Adenovirus E1A Proteins
-
Cyclin E
-
Nuclear Proteins
-
Oncogene Proteins
-
Saccharomyces cerevisiae Proteins
-
Trans-Activators
-
Acetyltransferases
-
CREB-Binding Protein
-
Crebbp protein, mouse
-
Histone Acetyltransferases
-
Protein Serine-Threonine Kinases
-
CDC2-CDC28 Kinases
-
Cdk2 protein, mouse
-
Cyclin-Dependent Kinase 2
-
Cyclin-Dependent Kinases