HIPK2 Controls Cytokinesis and Prevents Tetraploidization by Phosphorylating Histone H2B at the Midbody

Cinzia Rinaldo, Alice Moncada, Alessandra Gradi, Laura Ciuffini, Donatella D'Eliseo, Francesca Siepi, Andrea Prodosmo, Alessandra Giorgi, Giovanna M. Pierantoni, Francesco Trapasso, Giulia Guarguaglini, Armando Bartolazzi, Enrico Cundari, M. Eugenia Schininà, Alfredo Fusco, Silvia Soddu

Research output: Contribution to journalArticle

Abstract

Failure in cytokinesis, the final step in cell division, by generating tetra- and polyploidization promotes chromosomal instability, a hallmark of cancer. Here we show that HIPK2, a kinase involved in cell fate decisions in development and response to stress, controls cytokinesis and prevents tetraploidization through its effects on histone H2B. HIPK2 binds and phosphorylates histone H2B at S14 (H2B-S14 P), and the two proteins colocalize at the midbody. HIPK2 depletion by targeted gene disruption or RNA interference results in loss of H2B-S14 P at the midbody, prevention of cell cleavage, and tetra- and polyploidization. In HIPK2 null cells, restoration of wild-type HIPK2 activity or expression of a phosphomimetic H2B-S14D derivative abolishes cytokinesis defects and rescues cell proliferation, showing that H2B-S14 P is required for a faithful cytokinesis. Overall, our data uncover mechanisms of a critical HIPK2 function in cytokinesis and in the prevention of tetraploidization.

Original languageEnglish
Pages (from-to)87-98
Number of pages12
JournalMolecular Cell
Volume47
Issue number1
DOIs
Publication statusPublished - Jul 13 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Rinaldo, C., Moncada, A., Gradi, A., Ciuffini, L., D'Eliseo, D., Siepi, F., Prodosmo, A., Giorgi, A., Pierantoni, G. M., Trapasso, F., Guarguaglini, G., Bartolazzi, A., Cundari, E., Schininà, M. E., Fusco, A., & Soddu, S. (2012). HIPK2 Controls Cytokinesis and Prevents Tetraploidization by Phosphorylating Histone H2B at the Midbody. Molecular Cell, 47(1), 87-98. https://doi.org/10.1016/j.molcel.2012.04.029