Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP

The 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellula...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 1995-03, Vol.374 (6517), p.85-88
Main Authors: LUNDBLAD, J. R, KWOK, R. P. S, LAURANCE, M. E, HARTER, M. L, GOODMAN, R. H
Format: Article
Language:English
Subjects:
adenovirus
Adenovirus E1A Proteins - metabolism
Amino Acid Sequence
Biological and medical sciences
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cellular biology
CREB-Binding Protein
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
E1A-Associated p300 Protein
Fundamental and applied biological sciences. Psychology
Genetics
Inactivation
Molecular and cellular biology
Molecular Sequence Data
Nuclear Proteins - metabolism
Phosphorylation
Protein Binding
Proteins
Sequence Homology, Amino Acid
Trans-Activators
Transcription Factors - metabolism
Transcriptional Activation
Tumor Cells, Cultured
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral E1A-associated cellular protein p300 (refs 2, 3), and to two hypothetical proteins from Caenorhabditis elegans, R10E11.1 and K03H1.10 (refs 4 and 5, respectively), whose functions are unknown. Here, we show that CBP and p300 have similar binding affinity for the PKA-phosphorylated form of CREB, and that p300 can substitute for CBP in potentiating CREB-activated gene expression. We find that E1A binds to CBP through a domain conserved with p300 and represses the CREB-dependent co-activator functions of both CBP and p300. Our results indicate that the gene repression and cell immortalization functions associated with E1A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.
ISSN:0028-0836
1476-4687