Sharp-1 modulates the cellular response to DNA damage

FEBS Lett. 2010 Feb 5;584(3):619-24. doi: 10.1016/j.febslet.2009.12.011. Epub 2009 Dec 17.

Abstract

DNA damage checkpoints are essential for maintenance of genome integrity. We report here that inducible overexpression of the transcription factor Sharp-1 results in an S and G2/M cell cycle arrest, concomitant with the upregulation of Brca1 and GADD45alpha expression. In addition, we show that endogenous Sharp-1 mRNA is increased by DNA-damaging agents. Consistently, Sharp-1 overexpressing cells exhibit reduced apoptosis in response to chemotherapeutic drugs along with lower p53 expression and activity. Our studies identify a novel function for Sharp-1 in cell cycle arrest and DNA damage-induced apoptosis. Inappropriate Sharp-1 expression may therefore be associated with tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / genetics
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics
  • Cisplatin / pharmacology
  • DNA Damage / drug effects
  • DNA Damage / genetics*
  • Etoposide / pharmacology
  • Fluorouracil / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BRCA1 Protein
  • Bhlhb3 protein, mouse
  • Cell Cycle Proteins
  • Gadd45a protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Etoposide
  • Caspase 3
  • Cisplatin
  • Fluorouracil