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c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.

Publication ,  Journal Article
Chandramohan, V; Mineva, ND; Burke, B; Jeay, S; Wu, M; Shen, J; Yang, W; Hann, SR; Sonenshein, GE
Published in: J Cell Biochem
August 15, 2008

The p27(Kip1) (p27) cyclin-dependent kinase inhibitor and c-Myc oncoprotein play essential roles in control of cell cycle progression and apoptosis. Induction of p27 (CDKN1B) gene transcription by Forkhead box O proteins such as FOXO3a leads to growth arrest and apoptosis. Previously, we observed that B cell receptor (surface IgM) engagement of WEHI 231 immature B lymphoma cells with an anti-IgM antibody results in activation of FOXO3a, growth arrest and apoptosis. As ectopic c-Myc expression in these cells prevented anti-IgM induction of p27 and cell death, we hypothesized that c-Myc represses FOXO3a-mediated transcription. Here we show that c-Myc inhibits FOXO3a-mediated activation of the p27 promoter in multiple cell lines. The mechanism of this repression was explored using a combination of co-immunoprecipitation, oligonucleotide precipitation, and chromatin immunoprecipitation experiments. The studies demonstrate a functional association of FOXO3a and c-Myc on a proximal Forkhead binding element in the p27 promoter. This association involves the Myc box II domain of c-Myc and the N-terminal DNA-binding portion of FOXO3a. Analysis of publicly available microarray datasets showed an inverse pattern of c-MYC and p27 RNA expression in primary acute myeloid leukemia, prostate cancer and tongue squamous cell carcinoma samples. The inhibition of FOXO3a-mediated activation of the p27 gene by the high aberrant expression of c-Myc in many tumor cells likely contributes to their uncontrolled proliferation and invasive phenotype.

Duke Scholars

Published In

J Cell Biochem

DOI

EISSN

1097-4644

Publication Date

August 15, 2008

Volume

104

Issue

6

Start / End Page

2091 / 2106

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Repressor Proteins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Protein Structure, Tertiary
  • Protein Binding
  • Promoter Regions, Genetic
  • Neoplasms
  • Mice
  • Humans
 

Citation

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Chandramohan, V., Mineva, N. D., Burke, B., Jeay, S., Wu, M., Shen, J., … Sonenshein, G. E. (2008). c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. J Cell Biochem, 104(6), 2091–2106. https://doi.org/10.1002/jcb.21765
Chandramohan, Vidyalakshmi, Nora D. Mineva, Brian Burke, Sébastien Jeay, Min Wu, Jian Shen, William Yang, Stephen R. Hann, and Gail E. Sonenshein. “c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.J Cell Biochem 104, no. 6 (August 15, 2008): 2091–2106. https://doi.org/10.1002/jcb.21765.
Chandramohan V, Mineva ND, Burke B, Jeay S, Wu M, Shen J, et al. c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. J Cell Biochem. 2008 Aug 15;104(6):2091–106.
Chandramohan, Vidyalakshmi, et al. “c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.J Cell Biochem, vol. 104, no. 6, Aug. 2008, pp. 2091–106. Pubmed, doi:10.1002/jcb.21765.
Chandramohan V, Mineva ND, Burke B, Jeay S, Wu M, Shen J, Yang W, Hann SR, Sonenshein GE. c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. J Cell Biochem. 2008 Aug 15;104(6):2091–2106.
Journal cover image

Published In

J Cell Biochem

DOI

EISSN

1097-4644

Publication Date

August 15, 2008

Volume

104

Issue

6

Start / End Page

2091 / 2106

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Repressor Proteins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-myc
  • Protein Structure, Tertiary
  • Protein Binding
  • Promoter Regions, Genetic
  • Neoplasms
  • Mice
  • Humans