Glucocorticoid-induced Leucine Zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner

Perle Latré De Laté, Aurélie Pépin, Hind Assaf-Vandecasteele, Christophe Espinasse, Valérie Nicolas, Marie Liesse Asselin-Labat, Jacques Bertoglio, Marc Pallardy, Armelle Biola-Vidamment

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

GILZ (glucocorticoid-induced leucine zipper) is an ubiquitous protein whose expression is induced by glucocorticoids in lymphoid cells. We previously showed that GILZ expression is rapidly induced upon interleukin 2 deprivation in T-cells, protecting cells from apoptosis induced by forkhead box subgroup O3 (FOXO3). The aim of this work is to elucidate the molecular mechanism of FOXO factor inhibition by GILZ. We show in the myeloid cell line HL-60 and the lymphoid CTLL-2 T-cell line that GILZ down-regulates the expression of p27 KIP1 and Bim, two FOXO targets involved in cell cycle regulation and apoptosis, respectively. GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. This inhibitory effect is independent of protein kinase B and IΚB kinase phosphorylation sites. GILZ does not hinder FOXO3 DNA-binding activity and does not physically interact with FOXO3. However, using fluorescence microscopy, we observe that GILZ expression provokes a Crm-1-dependent nuclear exclusion of FOXO3 leading to its relocalization to the cytoplasm. Moreover, GILZ exclusive cytoplasmic localization is a prerequisite for FOXO3 inhibition and relocalization. We propose that GILZ is a general inhibitor of FOXO factors acting through an original mechanism by preventing them from reaching target genes within the nucleus.

Original languageEnglish (US)
Pages (from-to)5594-5605
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number8
DOIs
StatePublished - Feb 19 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Glucocorticoid-induced Leucine Zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner'. Together they form a unique fingerprint.

  • Cite this

    De Laté, P. L., Pépin, A., Assaf-Vandecasteele, H., Espinasse, C., Nicolas, V., Asselin-Labat, M. L., Bertoglio, J., Pallardy, M., & Biola-Vidamment, A. (2010). Glucocorticoid-induced Leucine Zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner. Journal of Biological Chemistry, 285(8), 5594-5605. https://doi.org/10.1074/jbc.M109.068346