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Publication : The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis.

First Author  Saurin AT Year  2008
Journal  Nat Cell Biol Volume  10
Issue  8 Pages  891-901
PubMed ID  18604201 Mgi Jnum  J:180456
Mgi Id  MGI:5306290 Doi  10.1038/ncb1749
Citation  Saurin AT, et al. (2008) The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis. Nat Cell Biol 10(8):891-901
abstractText  The cell cycle is exquisitely controlled by multiple sequential regulatory inputs to ensure fidelity. Here we demonstrate that the final step in division, the physical separation of daughter cells, is controlled by a member of the PKC gene superfamily. Specifically, we have identified three phosphorylation sites within PKCepsilon that control its association with 14-3-3. These phosphorylations are executed by p38 MAP kinase (Ser 350), GSK3 (Ser 346) and PKC itself (Ser 368). Integration of these signals is essential during mitosis because mutations that prevent phosphorylation of PKCepsilon and/or PKCepsilon binding to 14-3-3 also cause defects in the completion of cytokinesis. Using chemical genetic and dominant-negative approaches it is shown that selective inhibition of PKCepsilon halts cells at the final stages of separation. This arrest is associated with persistent RhoA activation at the midbody and a delay in actomyosin ring dissociation. This study therefore identifies a new regulatory mechanism that controls exit from cytokinesis, which has implications for carcinogenesis.
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