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HIPK2 controls cytokinesis and prevents tetraploidization by phosphorylating histone H2B at the midbody.
- Source :
-
Molecular cell [Mol Cell] 2012 Jul 13; Vol. 47 (1), pp. 87-98. Date of Electronic Publication: 2012 May 31. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Carrier Proteins genetics
Cell Division
Cell Line
Cell Line, Tumor
Embryo, Mammalian cytology
Fibroblasts cytology
Fibroblasts metabolism
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
HEK293 Cells
HeLa Cells
Histones genetics
Humans
Mice
Mice, Knockout
Microscopy, Fluorescence
Phosphorylation
Protein Binding
Protein Serine-Threonine Kinases genetics
RNA Interference
Tetraploidy
Carrier Proteins metabolism
Cytokinesis
Histones metabolism
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 47
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 22658722
- Full Text :
- https://doi.org/10.1016/j.molcel.2012.04.029