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NFBD1/MDC1 associates with p53 and regulates its function at the crossroad between cell survival and death in

Mitsuru Nakanishi1, Toshinori Ozaki, Hideki Yamamoto

  • 1Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

The Journal of Biological Chemistry
|May 31, 2007
PubMed

Insights

NFBD1/MDC1 protein prevents programmed cell death by inhibiting p53 phosphorylation, promoting cell survival after DNA damage. It binds p53, suppressing its activity and transcriptional functions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • NFBD1/MDC1, a BRCT superfamily member, exhibits anti-apoptotic activity.
  • It plays a role in early cellular responses to DNA damage.

Purpose of the Study:

  • To investigate the role of NFBD1 in regulating p53 activity and cell fate following DNA damage.
  • To elucidate the mechanism by which NFBD1 influences p53 phosphorylation and transcriptional activity.

Main Methods:

  • Small interference RNA (siRNA) mediated knockdown.
  • Immunoprecipitation assays.
  • Luciferase reporter assays.
  • Western blotting to assess p53 phosphorylation.

Main Results:

  • NFBD1 inhibits p53 phosphorylation at Ser-15, blocking its transcriptional and pro-apoptotic activities.
  • NFBD1 levels decrease in dying cells during the late phase of DNA damage.
  • NFBD1 knockdown increases adriamycin sensitivity in wild-type p53 cells but not in p53-deficient cells.
  • NFBD1 directly binds to the N-terminal region of p53, inhibiting its transcriptional activity.

Conclusions:

  • NFBD1 is a key regulator of cell survival and death decisions after DNA damage.
  • NFBD1 functions by modulating p53 activity through direct interaction and inhibition of phosphorylation.
  • The BRCT domains of NFBD1 are crucial for its interaction with p53 and suppression of p53-mediated transcriptional responses.

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