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Updated: Jul 14, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Nucleocytoplasmic shuttling of BID is involved in regulating its activities in the DNA-damage response

G Oberkovitz1, L Regev, A Gross

  • 1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Cell Death and Differentiation
|June 23, 2007
PubMed

Insights

The BH3-only BID protein, crucial for DNA damage response, exits the nucleus after treatment. Preventing its nuclear export blocks cell cycle arrest and death, suggesting BID

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The BH3-only BID protein integrates death signals into the apoptotic pathway.
  • BID phosphorylation by ATM kinase regulates its S-phase arrest and cell death functions.
  • Previous studies indicated nuclear localization of a portion of cellular BID.

Purpose of the Study:

  • To investigate the role of BID's nucleocytoplasmic shuttling in the DNA damage response.
  • To determine if nuclear export of BID is essential for its functions following DNA damage.

Main Methods:

  • Utilized etoposide and ionizing radiation to induce DNA damage.
  • Employed leptomycin B to inhibit CRM1-mediated nuclear export.
  • Generated a nuclear-localized BID variant (NLS-BID) by fusing it to a nuclear localization signal (NLS).
  • Assessed S-phase arrest and cell death in BID-deficient cells reconstituted with wild-type BID or NLS-BID.

Main Results:

  • Etoposide and ionizing radiation induced BID nuclear export, which was blocked by leptomycin B.
  • NLS-BID remained in the nucleus following etoposide treatment but was phosphorylated similarly to wild-type BID.
  • NLS-BID failed to restore S-phase arrest and etoposide-induced cell death in BID-deficient cells.

Conclusions:

  • BID's nuclear export is induced by DNA damage.
  • The nuclear export of BID is critical for its role in S-phase arrest and cell death.
  • Nucleocytoplasmic shuttling of BID may regulate its function in DNA damage response pathways.

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