A novel mechanism of cell growth regulation by Cell Cycle and Apoptosis Regulatory Protein (CARP)-1

Yan Jiang, Vineshkumar T Puliyappadamba, Liyue Zhang, Wenjuan Wu, Anil Wali, Michael B Yaffe, Joseph A Fontana, Arun K Rishi

Abstract

Background: CARP-1/CCAR1, a perinuclear phospho-protein, regulates signaling by adriamycin, steroids, or growth factors. However, intracellular events that regulate CARP-1-dependent cell growth are not fully understood.

Results: Here we investigated whether CARP-1 is involved in signaling induced by the protein kinase A inhibitor H89. Treatments of human breast cancer cells with H89 resulted in apoptosis that involved enhanced CARP-1 threonine phosphorylation and expression. Depletion of CARP-1, on the other hand, abrogates apoptosis induced by H89. CARP- 1 binds with signal transducer TAZ and over-expression of TAZ inhibits apoptosis by CARP-1. CARP-1 (651-759) interacts with a novel, N-terminal epitope of TAZ. H89 treatment stimulates threonine phosphorylation of CARP-1 (651-759), while substitution of threonine667 to alanine interferes with its binding with TAZ and apoptosis by H89. In addition, expression of wild type or CARP-1 (651-759) causes loss of c-myc expression due, in part, to suppression of c-myc transcription.

Conclusions: CARP-1 threonine667 regulates H89-dependent signaling by a novel pathway that involves modulation of CARP-1 interaction with TAZ and transcriptional down-regulation of c-myc.


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How to cite: Jiang, Y, Puliyappadamba, V.T., Zhang, L, Wu, W, Wali, A, Yaffe, M.B., Fontana, J.A. and Rishi, A.K. 2010. A novel mechanism of cell growth regulation by Cell Cycle and Apoptosis Regulatory Protein (CARP)-1. Journal of Molecular Signaling 5:7, DOI: http://dx.doi.org/10.1186/1750-2187-5-7

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This article has been peer reviewed (journal peer review policy).

Published on 1 July 2010.

ISSN: 1750-2187 | Published by Ubiquity Press | Creative Commons License This work is licensed under a Creative Commons License.