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

James Lundblad, Roland P S Kwok, Megan E. Laurance, Marian L. Harter, Richard Goodman

Research output: Contribution to journalArticle

508 Citations (Scopus)

Abstract

THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB1. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-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 El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.

Original languageEnglish (US)
Pages (from-to)85-88
Number of pages4
JournalNature
Volume374
Issue number6517
StatePublished - 1995

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Cyclic AMP-Dependent Protein Kinases
Caenorhabditis elegans Proteins
Activator Appliances
CREB-Binding Protein
Gene Expression
Second Messenger Systems
Transcriptional Activation
Carrier Proteins
Proteins
Transcription Factors
Genes

ASJC Scopus subject areas

  • General

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Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. / Lundblad, James; Kwok, Roland P S; Laurance, Megan E.; Harter, Marian L.; Goodman, Richard.

In: Nature, Vol. 374, No. 6517, 1995, p. 85-88.

Research output: Contribution to journalArticle

Lundblad, James ; Kwok, Roland P S ; Laurance, Megan E. ; Harter, Marian L. ; Goodman, Richard. / Adenoviral ElA-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. In: Nature. 1995 ; Vol. 374, No. 6517. pp. 85-88.
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abstract = "THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB1. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-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 El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.",
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AU - Kwok, Roland P S

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AU - Harter, Marian L.

AU - Goodman, Richard

PY - 1995

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N2 - THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB1. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-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 El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.

AB - THE 265K nuclear protein CBP was initially identified as a co-activator for the protein kinase A (PKA)-phosphorylated form of the transcription factor CREB1. The domains in CBP that are involved in CREB binding and transcriptional activation are highly related to the adenoviral ElA-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 El A involve the inactivation of a family of related proteins that normally participate in second-messenger-regulated gene expression.

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