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

Publication ,  Journal Article
Esmaili, AM; Johnson, EL; Thaivalappil, SS; Kuhn, HM; Kornbluth, S; Irusta, PM
Published in: Cell cycle (Georgetown, Tex.)
October 2010

Aven is a regulator of apoptosis whose overexpression is associated with poor prognosis in several cancers, including childhood acute lymphoblastic leukemia and acute myeloid leukemia. We have recently shown that Aven serves as an activator and substrate of ATM, thereby modulating the DNA-damage response and G(2)/M cell cycle progression. Under physiological conditions, the cellular localization of Aven is mainly cytosolic, but a small fraction of the protein is present in the nucleus. Here, we show that treatment of cells with leptomycin B, an inhibitor of Exportin-1/CRM (chromosomal region maintenance) 1, resulted in nuclear accumulation of Aven. Furthermore, we identified a functional LR-NES between amino acid residues 282-292 of the human Aven protein, a sequence that is evolutionary conserved among a range of vertebrate species. Disruption of this LR-NES by site-directed mutagenesis resulted in enhanced nuclear localization of Aven, but did not alter the ability of the protein to induce G(2)/M cell cycle arrest in interphase Xenopus laevis extracts. However, elimination of the LR-NES sequence led to a reduction in the capacity of Aven to arrest Xenopus oocytes containing intact nuclei. Our results suggest that the regulation of nucleocytoplasmatic traffic of Aven could modulate its ability to influence cell cycle progression.

Duke Scholars

Published In

Cell cycle (Georgetown, Tex.)

DOI

EISSN

1551-4005

ISSN

1538-4101

Publication Date

October 2010

Volume

9

Issue

19

Start / End Page

3913 / 3920

Related Subject Headings

  • Xenopus laevis
  • Sequence Alignment
  • Receptors, Cytoplasmic and Nuclear
  • Oocytes
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Membrane Proteins
  • Karyopherins
  • Humans
  • Hela Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Esmaili, A. M., Johnson, E. L., Thaivalappil, S. S., Kuhn, H. M., Kornbluth, S., & Irusta, P. M. (2010). Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export. Cell Cycle (Georgetown, Tex.), 9(19), 3913–3920. https://doi.org/10.4161/cc.9.19.13138
Esmaili, Armond M., Erika L. Johnson, Silpa S. Thaivalappil, Helena M. Kuhn, Sally Kornbluth, and Pablo M. Irusta. “Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.Cell Cycle (Georgetown, Tex.) 9, no. 19 (October 2010): 3913–20. https://doi.org/10.4161/cc.9.19.13138.
Esmaili AM, Johnson EL, Thaivalappil SS, Kuhn HM, Kornbluth S, Irusta PM. Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export. Cell cycle (Georgetown, Tex). 2010 Oct;9(19):3913–20.
Esmaili, Armond M., et al. “Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.Cell Cycle (Georgetown, Tex.), vol. 9, no. 19, Oct. 2010, pp. 3913–20. Epmc, doi:10.4161/cc.9.19.13138.
Esmaili AM, Johnson EL, Thaivalappil SS, Kuhn HM, Kornbluth S, Irusta PM. Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export. Cell cycle (Georgetown, Tex). 2010 Oct;9(19):3913–3920.

Published In

Cell cycle (Georgetown, Tex.)

DOI

EISSN

1551-4005

ISSN

1538-4101

Publication Date

October 2010

Volume

9

Issue

19

Start / End Page

3913 / 3920

Related Subject Headings

  • Xenopus laevis
  • Sequence Alignment
  • Receptors, Cytoplasmic and Nuclear
  • Oocytes
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Membrane Proteins
  • Karyopherins
  • Humans
  • Hela Cells