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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5130-5140. Prepublished online as a Blood First Edition Paper on September 17, 2008; DOI 10.1182/blood-2007-12-128744. This Article Full Text (PDF) All Versions of this Article: blood-2007-12-128744v1 112/13/5130    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Heuze, M. L Articles by Lutz, P. G Search for Related Content PubMed PubMed Citation Articles by Heuze, M. L Articles by Lutz, P. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 12, 2007 Accepted August 20, 2008 ASB2 targets filamins A and B to proteasomal degradation Melina L Heuze, Isabelle Lamsoul, Massimiliano Baldassarre, Yatish Lad, Sophie Leveque, Ziba Razinia, Christel Moog-Lutz, David A Calderwood, and Pierre G Lutz* Universite de Toulouse, UPS, Toulouse, France Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, Toulouse, France Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT, United States Department of Cell Biology, Yale University School of Medicine, New Haven, CT, United States Universite Pierre et Marie Curie, Paris, France * Corresponding author; email: pierre.lutz{at}ipbs.fr. The ordered series of proliferation and differentiation from hematopoietic progenitor cells is disrupted in leukemia resulting in arrest of differentiation at immature proliferative stages. Characterizing the molecular basis of hematopoietic differentiation is therefore important for understanding and treating disease. Retinoic acid induces expression of Ankyrin repeat-containing protein with a Suppressor of Cytokine signaling Box 2 (ASB2) in acute promyelocytic leukemia cells and ASB2 expression inhibits growth and promotes commitment, recapitulating an early step critical for differentiation. ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins, however no ASB2 substrates had been identified. Here we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation. Knockdown of endogenous ASB2 in leukemia cells delays retinoic acid-induced differentiation and filamin degradation, conversely ASB2 expression in leukemia cells induces filamin degradation. ASB2 expression inhibits cell spreading and this effect is recapitulated by knocking down both filamin A and filamin B. Thus, we suggest that ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins for degradation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. K. Heikkinen, S. Ruskamo, P. V. Konarev, D. I. Svergun, T. Iivanainen, S. M. Heikkinen, P. Permi, H. Koskela, I. Kilpelainen, and J. Ylanne Atomic Structures of Two Novel Immunoglobulin-like Domain Pairs in the Actin Cross-linking Protein Filamin J. Biol. Chem., September 11, 2009; 284(37): 25450 - 25458. [Abstract] [Full Text] [PDF] C. F. Burande, M. L. Heuze, I. Lamsoul, B. Monsarrat, S. Uttenweiler-Joseph, and P. G. Lutz A Label-free Quantitative Proteomics Strategy to Identify E3 Ubiquitin Ligase Substrates Targeted to Proteasome Degradation Mol. Cell. Proteomics, July 1, 2009; 8(7): 1719 - 1727. [Abstract] [Full Text] [PDF]

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