Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation

  • Authors:
    • Howard E. Boudreau
    • Constantinos G. Broustas
    • Prafulla C. Gokhale
    • Deepak Kumar
    • Rajshree R. Mewani
    • Janice D. Rone
    • Bassem R. Haddad
    • Usha Kasid
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijmm.19.1.29
  • Pages: 29-39
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Abstract

Raf-1 protein serine/threonine kinase plays an important role in ERK signal transduction pathway of cell survival and proliferation. Raf-induced transcriptional changes are dependent on phosphorylation/activation of ERK. However, regulation of phospho-ERK (p-ERK) via Raf transcriptome is as yet unknown. We report the initial characterization of BRCC3, a novel gene discovered previously by mRNA expression profiling in MDA-MB 231 human breast cancer cells treated with Raf antisense oligonucleotide. BRCC3 is localized at human chromosome 5q12.1. BRCC3 open reading frame consists of 529 amino acids, coding for an approximate 60-kDa predominantly membrane-associated protein. Expression levels of BRCC3 mRNA and protein are high during G2/M phase of the cell cycle in breast cancer cells. Treatment of MDA-MB 231 cells with Raf-1 siRNA resulted in decreased expression of Raf-1, BRCC3 and p-ERK, but not B-Raf. Transient or stable expression of the epitope-tagged BRCC3 cDNA was associated with increased p-ERK in three different cell lines. Consistently, BRCC3 siRNA treatment of MDA-MB 231 cells caused decreased expression of BRCC3 and p-ERK. Furthermore, exogenous BRCC3 expression was associated with a delay in etoposide-induced cell death and an increase in cell proliferation. These findings demonstrate that BRCC3 is a novel effector of Raf-1, and implicate a role of BRCC3 in modulation of p-ERK, cell survival and proliferation.

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January 2007
Volume 19 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Boudreau HE, Broustas CG, Gokhale PC, Kumar D, Mewani RR, Rone JD, Haddad BR and Kasid U: Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation. Int J Mol Med 19: 29-39, 2007.
APA
Boudreau, H.E., Broustas, C.G., Gokhale, P.C., Kumar, D., Mewani, R.R., Rone, J.D. ... Kasid, U. (2007). Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation. International Journal of Molecular Medicine, 19, 29-39. https://doi.org/10.3892/ijmm.19.1.29
MLA
Boudreau, H. E., Broustas, C. G., Gokhale, P. C., Kumar, D., Mewani, R. R., Rone, J. D., Haddad, B. R., Kasid, U."Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation". International Journal of Molecular Medicine 19.1 (2007): 29-39.
Chicago
Boudreau, H. E., Broustas, C. G., Gokhale, P. C., Kumar, D., Mewani, R. R., Rone, J. D., Haddad, B. R., Kasid, U."Expression of BRCC3, a novel cell cycle regulated molecule, is associated with increased phospho-ERK and cell proliferation". International Journal of Molecular Medicine 19, no. 1 (2007): 29-39. https://doi.org/10.3892/ijmm.19.1.29