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Download hipk2 phosphorylates histone h2b at the midbody to allow cytokinesis
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HIPK2: Cytokinesis,Tetraploidization and Cancer D. Valente Rinaldo (1,2) (1,2) , F. Magi(1,2),G.M. Pierantoni(3), A. Fusco(3) ,S. Soddu(2) and C. (1) IBPM CNR, Rome, Italy (2) Regina Elena Cancer Institute, Rome, Italy (3) IEOS CNR, Naples Italy We have recently demonstrated that the Serine/Threonine kinase HIPK2, an oncosuppressor involved in cell proliferation and apoptosis, controls cytokinesis and prevents tetraploidization. In particular, we showed that HIPK2 binds and phosphorylates histone H2B at Serine14 (H2B-S14P) and the two proteins co-localize at the midbody. HIPK2 depletion results in loss of H2B-S14P at midbody, prevention of cell cleavage at the end of mitosis, tetra- and poly-ploidization. In HIPK2-null cells, expression of wild-type HIPK2 but not of its kinase-defective mutant restores H2B-S14P at midbody and abolishes cytokinesis defects. Strikingly, a similar rescue is promoted by the sole expression of a phosphomimetic H2B-S14D mutant, indicating that HIPK2-mediated H2B-S14 phosphorylation is required for faithful cytokinesis. This HIPK2 unexpected function highlights the possibility that the oncosupressor activity of HIPK2 is not only linked to its pro-apoptotic function, but also to cytokinesis control. We are now investigating whether HIPK2 dysfunctions may contribute to CIN and tumorigenesis by using in vitro and in vivo murine models.
