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Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export

Armond M Esmaili1, Erika L Johnson, Silpa S Thaivalappil

  • 1Department of Human Science, Georgetown University Medical Center, Washington, DC, USA.

Cell Cycle (Georgetown, Tex.)
|October 12, 2010
PubMed

Insights

Aven protein

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Aven regulates apoptosis and is overexpressed in cancers like leukemia.
  • Aven is an activator and substrate of ATM, impacting DNA damage response and cell cycle.
  • Aven is primarily cytosolic but has some nuclear presence.

Purpose of the Study:

  • To investigate the regulation of Aven's nucleocytoplasmic transport.
  • To determine if Aven's localization affects its cell cycle regulatory function.

Main Methods:

  • Cells were treated with leptomycin B, an Exportin-1 inhibitor.
  • A functional nuclear export signal (NES) in Aven was identified and mutated.
  • Aven's localization and cell cycle arrest capabilities were assessed in Xenopus extracts and oocytes.

Main Results:

  • Leptomycin B treatment caused nuclear accumulation of Aven.
  • A conserved nuclear export signal (LR-NES) between residues 282-292 was identified.
  • Mutating the LR-NES enhanced nuclear localization but did not affect G(2)/M arrest in extracts.
  • Eliminating the LR-NES reduced Aven's ability to arrest oocytes.

Conclusions:

  • Nucleocytoplasmic transport of Aven is regulated by a specific NES.
  • Aven's localization influences its function in cell cycle progression, particularly in intact cells.

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