c-Myb regulates cell cycle-dependent expression of Erbin: an implication for a novel function of Erbin

PLoS One. 2012;7(8):e42903. doi: 10.1371/journal.pone.0042903. Epub 2012 Aug 7.

Abstract

In the present study, we demonstrated the cell cycle periodicity of Erbin expression with the maximal expression of Erbin in G2/M phase. A significant increase in Erbin promoter activity was observed in G2/M phase-synchronized cells. Sequence analysis revealed a c-Myb site in the core promoter region of Erbin. Mutagenesis of c-Myb consensus sequences abrogated the increased Erbin promoter activity in G2/M phase. ChIP and oligonucleotide pull-down assays validated that the recruitment of c-Myb to the consensus sequences was specific. The interaction of c-Myb with c-Myb site in the Erbin promoter was significantly enhanced in G2/M phase. Ectopic overexpression of c-Myb led to the up-regulation of Erbin promoter activity and c-Myb silencing by small interfering RNA significantly decreased Erbin protein level. Transfection of c-Myb rescued Erbin expression that was impaired by c-Myb knockdown. It proves that c-Myb and the c-Myb response element mediate the cell cycle-dependent expression of Erbin. Inactivation of Erbin causes an acceleration of the G1/S transition, the formation of multipolar spindles and abnormal chromosome congression. These results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M phase and also predict an unappreciated function of Erbin in cell cycle progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Base Sequence
  • Binding Sites
  • Cell Cycle*
  • Cell Line, Tumor
  • Consensus Sequence / genetics
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • ERBIN protein, human
  • Proto-Oncogene Proteins c-myb

Grants and funding

This work is supported by National Basic Research Program of China (973 Program, No. 2010CB911904), National Natural Science Foundation of China (No. 30800582 and 30972690) and Beijing National Natural Science Foundation (No. 7122124). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.