Impairment of cytokinesis by cancer-associated DAPK3 mutations

Death-associated protein kinase 3 (DAPK3), a member of the DAPK family, contributes to cytokinesis by phosphorylating myosin II regulatory light chain (MRLC). Missense mutations in DAPK3, T112M, D161N, and P216S, were observed in the lung, colon, and cervical cancers, respectively, but the effects o...

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Bibliographic Details
Published in:	Biochemical and biophysical research communications Vol. 533; no. 4; pp. 1095 - 1101
Main Authors:	Ono, Taichiro, Terada, Fumi, Okumura, Misako, Chihara, Takahiro, Hamao, Kozue
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 17-12-2020
Subjects:	Cancer-associated mutations Cytokinesis Cytokinesis - genetics DAPK3 Death-Associated Protein Kinases - genetics Death-Associated Protein Kinases - metabolism HeLa Cells Humans Mutation, Missense Myosin II regulatory Light chain Myosin Light Chains - metabolism Phosphorylation ZIPK Cancer-associated mutations DAPK3 MRLC P-MRLC Myosin II regulatory Light chain Cytokinesis TRITC
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Summary:	Death-associated protein kinase 3 (DAPK3), a member of the DAPK family, contributes to cytokinesis by phosphorylating myosin II regulatory light chain (MRLC). Missense mutations in DAPK3, T112M, D161N, and P216S, were observed in the lung, colon, and cervical cancers, respectively, but the effects of these mutations on cytokinesis remain unclear. Here, we show that cells expressing EGFP-DAPK3-T112M, -D161N, or -P216S exhibited reduced rates of cytokinesis, with an increased ratio of multinucleated cells. In addition, these cells exhibited reduced levels of phosphorylated MRLC at the contractile ring. Collectively, our data demonstrates that cancer-associated DAPK3 mutations impair cytokinesis by reducing phosphorylated MRLC. •Cells expressing cancer-associated DAPK3 mutants slow down cytokinesis.•Expression of DAPK3 mutants increases the ratio of multinucleate cells.•DAPK3 mutants reduce phosphorylated MRLC levels at the contractile ring.•DAPK3 mutations impair cytokinesis through MRLC phosphorylation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2020.09.078