Knockdown expression of Apc11 leads to cell-cycle distribution reduction in G2/M phase

Genet Mol Res. 2012 Aug 24;11(3):2814-22. doi: 10.4238/2012.August.24.6.

Abstract

Anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase in cell division, which catalyses ubiquitination of cell-cycle regulators. Studying this complex could reveal important information regarding its application in cancer research and therapy. In this study, 4 synthesized small interfering RNAs (siRNAs) were transfected into HEK293T cells to suppress messenger RNA (mRNA) of Apc11; 2 of these reduced the amount of Apc11 mRNA by over 50%. Further experiments showed that rather than causing apoptosis, siRNA transfection led to cell-cycle distributions characterized by less time spent in G2/M phase and more time spent in G1 phase. This phenomenon was specifically induced by Apc11 silencing, as co-transfection of siRNA and an Apc11 plasmid could reverse this distribution bias. Our results suggested that siRNA targeted against Apc11 could hamper entry into G2/M phase. Current efforts are focused on elucidating the function and utility of the APC complex for clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Cell Division*
  • G2 Phase*
  • Gene Knockdown Techniques*
  • HEK293 Cells
  • Humans
  • RNA, Small Interfering / metabolism
  • Transfection
  • Ubiquitin-Protein Ligase Complexes / metabolism*

Substances

  • RNA, Small Interfering
  • Ubiquitin-Protein Ligase Complexes
  • ANAPC11 protein, human
  • Anaphase-Promoting Complex-Cyclosome
  • Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome