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Báo cáo khoa học: The SWI⁄SNF protein BAF60b is ubiquitinated through a signalling process involving Rac GTPase and the RING finger protein Unkempt

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The SWI⁄SNF chromatin remodelling complexes are important regulators of transcription; they consist of large multisubunit assemblies containing either Brm or Brg1 as the catalytic ATPase subunit and a variable subset of approximately 10 Brg⁄Brm-associated factors (BAF). Among these factors, BAF60 proteins (BAF60a, BAF60b or BAF60c), which are found in most complexes, are thought to bridge interactions between transcription factors and SWI⁄SNF complexes. | The SWI SNF protein BAF60b is ubiquitinated through a signalling process involving Rac GTPase and the RING finger protein Unkempt Patrick Lorès1 2 Orane Visvikis1 2 Rosa Luna1 2 Emmanuel Lemichez3 4 and Gerard Gacon1 2 1 Institut Cochin Université Paris Descartes CNRS UMR8104 Paris France 2 INSERM U567 Paris France 3 INSERM U895 Centre Mediterraneen de Medecine Moleculaire C3M Toxines Microbiennes dans la relation hote pathogenes Nice France 4 Universite de Nice Sophia-Antipolis UFR Medecine Nice France Keywords BAF60 Rac GTPase RING finger SWI SNF complex ubiquitination Correspondence G. Gacon Departement Genetique et Developpement Institut Cochin 24 rue du Faubourg Saint-Jacques 75014 Paris France Fax 33 1 44 41 24 48 Tel 33 1 44 41 24 70 E-mail gerard.gacon@inserm.fr These authors contributed equally to this work Received 4 September 2009 revised 30 November 2009 accepted 8 January 2010 doi 10.1111 j.1742-4658.2010.07575.x The SWI SNF chromatin remodelling complexes are important regulators of transcription they consist of large multisubunit assemblies containing either Brm or Brg1 as the catalytic ATPase subunit and a variable subset of approximately 10 Brg Brm-associated factors BAF . Among these factors BAF60 proteins BAF60a BAF60b or BAF60c which are found in most complexes are thought to bridge interactions between transcription factors and SWI SNF complexes. We report here on a Rac-dependent process leading to BAF60b ubiquitination. Using two-hybrid cloning procedures we identified a mammalian RING finger protein homologous to drosophila Unkempt as a new partner of the activated form of RacGTPases and demonstrated that mammalian Unkempt specifically binds to BAF60b and promotes its ubiquitination in a Rac1-dependent manner. Immunofluorescence studies demonstrated that Unkempt is primarily localized in the cytoplasmic compartment but has the ability to shuttle between the nucleus and the cytoplasm suggesting that the Rac- and Unkempt-dependent process .

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