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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article number7
JournalJournal of Molecular Signaling
Volume5
DOIs
StatePublished - Jul 1 2010

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Cell Cycle Proteins
Apoptosis Regulatory Proteins
Cell growth
Growth
Apoptosis
Phosphorylation
Threonine
Transcription
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Transducers
Alanine
Doxorubicin
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Epitopes
Intercellular Signaling Peptides and Proteins
Substitution reactions
Down-Regulation
Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A novel mechanism of cell growth regulation by Cell Cycle and Apoptosis Regulatory Protein (CARP)-1. / Jiang, Yan; Puliyappadamba, Vineshkumar T.; Zhang, Liyue; Wu, Wenjuan; Wali, Anil; Yaffe, Michael B.; Fontana, Joseph A.; Rishi, Arun K.

In: Journal of Molecular Signaling, Vol. 5, 7, 01.07.2010.

Research output: Contribution to journalArticle

Jiang, Yan ; Puliyappadamba, Vineshkumar T. ; Zhang, Liyue ; Wu, Wenjuan ; Wali, Anil ; Yaffe, Michael B. ; Fontana, Joseph A. ; Rishi, Arun K. / A novel mechanism of cell growth regulation by Cell Cycle and Apoptosis Regulatory Protein (CARP)-1. In: Journal of Molecular Signaling. 2010 ; Vol. 5.
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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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