CBP as a transcriptional organizer

Richard Goodman, Ychen S. Smolik

Research output: Contribution to journalArticle

Abstract

The signal transduction events leading to the induction of cAMP-responsive genes constitute one of the best characterized transcriptional pathways. We have proposed that phosphorylation by PKA allows CREB to recruit a coactivator protein. CBP, that is responsible for transcriptional activation. This model has been extended by findings from other laboratories that many additional transcriptional activities also function through CBP. To date, most studies of CBP function have utilized cell culture models. To address the contribution of CBP to gene regulation in an intact system, we have examined its participation in the Drosophila hedgehog pathway. The transcription factor cubitus interruptus (ci) has been shown to depend on Drosophila CBP (dCBP) for activation. dCBP binds to the carboxy-terminal domain of ci, a portion that is removed by the proteolytic processing event that regulates ci function. PKA negatively regulates the hedgehog pathway, and we have shown that this modulation depends on ci phosphorylation. Phosphorylation of ci promotes proteolytic processing and removal of the dCBP interaction domain. Mutation of the PKA sites in ci prevents proteolytic processing and maintains the abil ity of ci to interact with dCBP. Thus, the negative regulation of transcription mediated by PKA in the Drosophila hedgehog pathway occurs indirectly by preventing dCBP recruitment to the promoters of ci-responsive genes.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998

Fingerprint

Phosphorylation
Drosophila
Processing
Genes
Hedgehogs
Chemical activation
Erinaceidae
Signal transduction
phosphorylation
Transcription
Cell culture
Gene expression
Transcription Factors
Modulation
genes
transcriptional activation
Proteins
Transcriptional Activation
signal transduction
Signal Transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

CBP as a transcriptional organizer. / Goodman, Richard; Smolik, Ychen S.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

Goodman, R & Smolik, YS 1998, 'CBP as a transcriptional organizer', FASEB Journal, vol. 12, no. 8.
Goodman, Richard ; Smolik, Ychen S. / CBP as a transcriptional organizer. In: FASEB Journal. 1998 ; Vol. 12, No. 8.
@article{db0a4043d16e48ef8d312482f83cc6c4,
title = "CBP as a transcriptional organizer",
abstract = "The signal transduction events leading to the induction of cAMP-responsive genes constitute one of the best characterized transcriptional pathways. We have proposed that phosphorylation by PKA allows CREB to recruit a coactivator protein. CBP, that is responsible for transcriptional activation. This model has been extended by findings from other laboratories that many additional transcriptional activities also function through CBP. To date, most studies of CBP function have utilized cell culture models. To address the contribution of CBP to gene regulation in an intact system, we have examined its participation in the Drosophila hedgehog pathway. The transcription factor cubitus interruptus (ci) has been shown to depend on Drosophila CBP (dCBP) for activation. dCBP binds to the carboxy-terminal domain of ci, a portion that is removed by the proteolytic processing event that regulates ci function. PKA negatively regulates the hedgehog pathway, and we have shown that this modulation depends on ci phosphorylation. Phosphorylation of ci promotes proteolytic processing and removal of the dCBP interaction domain. Mutation of the PKA sites in ci prevents proteolytic processing and maintains the abil ity of ci to interact with dCBP. Thus, the negative regulation of transcription mediated by PKA in the Drosophila hedgehog pathway occurs indirectly by preventing dCBP recruitment to the promoters of ci-responsive genes.",
author = "Richard Goodman and Smolik, {Ychen S.}",
year = "1998",
language = "English (US)",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

TY - JOUR

T1 - CBP as a transcriptional organizer

AU - Goodman, Richard

AU - Smolik, Ychen S.

PY - 1998

Y1 - 1998

N2 - The signal transduction events leading to the induction of cAMP-responsive genes constitute one of the best characterized transcriptional pathways. We have proposed that phosphorylation by PKA allows CREB to recruit a coactivator protein. CBP, that is responsible for transcriptional activation. This model has been extended by findings from other laboratories that many additional transcriptional activities also function through CBP. To date, most studies of CBP function have utilized cell culture models. To address the contribution of CBP to gene regulation in an intact system, we have examined its participation in the Drosophila hedgehog pathway. The transcription factor cubitus interruptus (ci) has been shown to depend on Drosophila CBP (dCBP) for activation. dCBP binds to the carboxy-terminal domain of ci, a portion that is removed by the proteolytic processing event that regulates ci function. PKA negatively regulates the hedgehog pathway, and we have shown that this modulation depends on ci phosphorylation. Phosphorylation of ci promotes proteolytic processing and removal of the dCBP interaction domain. Mutation of the PKA sites in ci prevents proteolytic processing and maintains the abil ity of ci to interact with dCBP. Thus, the negative regulation of transcription mediated by PKA in the Drosophila hedgehog pathway occurs indirectly by preventing dCBP recruitment to the promoters of ci-responsive genes.

AB - The signal transduction events leading to the induction of cAMP-responsive genes constitute one of the best characterized transcriptional pathways. We have proposed that phosphorylation by PKA allows CREB to recruit a coactivator protein. CBP, that is responsible for transcriptional activation. This model has been extended by findings from other laboratories that many additional transcriptional activities also function through CBP. To date, most studies of CBP function have utilized cell culture models. To address the contribution of CBP to gene regulation in an intact system, we have examined its participation in the Drosophila hedgehog pathway. The transcription factor cubitus interruptus (ci) has been shown to depend on Drosophila CBP (dCBP) for activation. dCBP binds to the carboxy-terminal domain of ci, a portion that is removed by the proteolytic processing event that regulates ci function. PKA negatively regulates the hedgehog pathway, and we have shown that this modulation depends on ci phosphorylation. Phosphorylation of ci promotes proteolytic processing and removal of the dCBP interaction domain. Mutation of the PKA sites in ci prevents proteolytic processing and maintains the abil ity of ci to interact with dCBP. Thus, the negative regulation of transcription mediated by PKA in the Drosophila hedgehog pathway occurs indirectly by preventing dCBP recruitment to the promoters of ci-responsive genes.

UR - http://www.scopus.com/inward/record.url?scp=33749089474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749089474&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749089474

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -