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Molecular and Cellular Biology, November 2005, p. 9427-9434, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9427-9434.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Gain-of-Function Allele of cbp-1, the Caenorhabditis elegans Ortholog of the Mammalian CBP/p300 Gene, Causes an Increase in Histone Acetyltransferase Activity and Antagonism of Activated Ras

Dennis J. Eastburn and Min Han^*

Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309-0347

Received 3 June 2005/ Returned for modification 28 July 2005/ Accepted 11 August 2005

An RTK-Ras-mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in vulval induction in Caenorhabditis elegans. We have previously carried out screens for suppressors of activated Ras to identify factors that play critical roles in the regulation of the pathway. ku258 was isolated as a semidominant allele that suppresses the Multivulva phenotype caused by activated let-60 ras. Our genetic and molecular analyses indicate that ku258 is a gain-of-function allele resulting from two point mutations in the C. elegans homolog of the transcriptional coactivator p300/CBP, cbp-1. Genetic data also suggest that cbp-1 may act downstream of the Ras signaling pathway, but not primarily downstream of the Wnt signaling pathway, to negatively regulate vulval cell fate specification. cbp-1 may function in concert with LIN-1, an Ets transcription factor family member that is one of the targets of MAPK. In vitro histone acetylation assays have revealed that together, the two point mutations cause a sevenfold increase in the histone acetyltransferase (HAT) activity of recombinant CBP-1. To our knowledge, this is the only such HAT activity mutation isolated in a CBP/p300 family protein, and this mutation may define a negative role of the HAT activity in antagonizing Ras function in a specific developmental event.

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* Corresponding author. Mailing address: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309-0347. Phone: (303) 492-2261. Fax: (303) 735-0175. E-mail: mhan{at}colorado.edu.

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Molecular and Cellular Biology, November 2005, p. 9427-9434, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9427-9434.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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