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Article Dans Une Revue Journal of Biological Chemistry Année : 2011

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

Isabelle Lamsoul
Clara Burande
  • Fonction : Auteur
Ziba Razinia
  • Fonction : Auteur
Massimiliano Baldassarre
  • Fonction : Auteur
David Calderwood
  • Fonction : Auteur
Pierre Lutz

Résumé

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.

Dates et versions

hal-02406517 , version 1 (12-12-2019)

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Citer

Isabelle Lamsoul, Clara Burande, Ziba Razinia, Thibault Houles, Delphine Menoret, et al.. Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells. Journal of Biological Chemistry, 2011, 286 (35), pp.30571-30581. ⟨10.1074/jbc.M111.220921⟩. ⟨hal-02406517⟩
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