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| Subject Categories: Cell & Tissue Architecture | Genome Stability & Dynamics |
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| The EMBO Journal
(2004) 23, 3758–3768, doi:10.1038/sj.emboj.7600403 Published online 23 September 2004 |
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| The membrane form of the DNA repair protein Ku interacts at the cell surface with metalloproteinase 9 |
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| Sylvie Monferran1, Jenny Paupert1, Stéphanie Dauvillier, Bernard Salles and Catherine Muller |
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Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Toulouse, France To whom correspondence should be addressed Bernard Salles, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex 04, France. Tel.: +33 5 61175936; Fax: +33 5 61175933; E-mail: bernard.salles@ipbs.fr 1 These authors contributed equally to this work Received 9 October 2003; Accepted 13 August 2004; Published online 23 September 2004. |
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| Abstract |
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| The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double-strand breaks repair. Ku is also expressed on the cell surface of different types of cells where its function remains poorly understood. From a yeast two-hybrid screen, we have identified a specific interaction between the core region of Ku80 and the hemopexin domain of metalloproteinase 9 (MMP-9), a key enzyme involved in the degradation of extracellular matrix (ECM) components. Ku associates with MMP-9 on the surface of leukemic cells as demonstrated by co-immunoprecipitation experiments in membrane extracts and double-label immunofluorescence studies. In normal and tumoral migratory cells, Ku80 and MMP-9 colocalize at the periphery of leading edge of cells and cellular invasion of collagen IV matrices was blocked by antibodies directed against Ku70 or Ku80 subunits as well as by Ku80-specific antisense oligonucleotides. Our results indicate that Ku and MMP-9 interact at the cell membrane of highly invasive hematopoietic cells of normal and tumoral origin and document the unexpected importance of the membrane-associated form of Ku in the regulation of ECM remodelling. |
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| Keywords: extracellular matrix, invasion, ku heterodimer, macrophages, metalloproteinase 9 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article Journal of Cerebral Blood Flow & Metabolism Original Article A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins Nature Immunology Article (01 Jun 2001) The EMBO Journal Article (01 Aug 2002) Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151 Laboratory Investigation Research Article |
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