Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells

Isabelle Lamsoul, Clara F Burande, Ziba Razinia, Thibault C Houles, Delphine Menoret, Massimiliano Baldassarre, Monique Erard, Christel Moog-Lutz, David A Calderwood, Pierre G Lutz

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

By providing contacts between hematopoietic cells and the bone marrow microenvironment, integrins are implicated in cell adhesion and thereby in control of cell fate of normal and leukemia cells. The ASB2 gene, initially identified as a retinoic acid responsive gene and a target of the promyelocytic leukemia retinoic acid receptor α oncoprotein in acute promyelocytic leukemia cells, encodes two isoforms, a hematopoietic-type (ASB2α) and a muscle-type (ASB2β) that are involved in hematopoietic and myogenic differentiation, respectively. ASB2α is the specificity subunit of an E3 ubiquitin ligase complex that targets filamins to proteasomal degradation. To examine the relationship of the ASB2α structure to E3 ubiquitin ligase function, functional assays and molecular modeling were performed. We show that ASB2α, through filamin A degradation, enhances adhesion of hematopoietic cells to fibronectin, the main ligand of β1 integrins. Furthermore, we demonstrate that a short N-terminal region specific to ASB2α, together with ankyrin repeats 1 to 10, is necessary for association of ASB2α with filamin A. Importantly, the ASB2α N-terminal region comprises a 9-residue segment with predicted structural homology to the filamin-binding motifs of migfilin and β integrins. Together, these data provide new insights into the molecular mechanisms of ASB2α binding to filamin.

Original languageEnglish
Pages (from-to)30571-30581
Number of pages11
JournalThe Journal of Biological Chemistry
Volume286
Issue number35
Early online date7 Jul 2011
DOIs
Publication statusPublished - 2 Sep 2011

Keywords

  • adaptor proteins, signal transducing
  • amino acid motifs
  • animals
  • carrier proteins
  • cell adhesion
  • fibronectins
  • gene expression regulation
  • hela cells
  • hematopoietic stem cells
  • humans
  • integrins
  • mice
  • muscles
  • NIH 3T3 cells
  • protein binding
  • protein structure, tertiary
  • substrate specificity
  • suppressor of cytokine signaling proteins

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    Lamsoul, I., Burande, C. F., Razinia, Z., Houles, T. C., Menoret, D., Baldassarre, M., Erard, M., Moog-Lutz, C., Calderwood, D. A., & Lutz, P. G. (2011). Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells. The Journal of Biological Chemistry, 286(35), 30571-30581. https://doi.org/10.1074/jbc.M111.220921