The Double Life of the Ku Protein: Facing the DNA Breaks and the Extracellular Environment

Abstract

The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double strand break recognitionand repair. It has been shown, more than ten years ago, that Ku is also expressed at the cellsurface of different cells types along with its intra-cellular pool within the nucleus and thecytoplasm but involvement of Ku in cell-cell and cell-extracellular matrix adhesion has beenonly recently demonstrated. In addition, we have shown that Ku may have a second andunexpected activity in cell/microenvironment interaction. Indeed, Ku appears to be involved inextra-cellular proteolytic processes through its specific interaction, on the cell surface, with thematrix metalloprotease 9. Taken together, these results suggest that Ku function at the cellsurface is likely to be important in tumour invasion. Various fundamental questions arise fromthese observations. How Ku is expressed on the cell surface, why a protein with completelyunrelated functions also serve as an « integrin like »molecule once expressed at the cell surfaceand is this functional moonlighting of Ku related to cell transformation remain open issues thatwill be discussed here.