The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells Journal Article
| Authors: | Berdougo, E.; Nachury, M. V.; Jackson, P. K.; Jallepalli, P. V. |
| Article Title: | The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells |
| Abstract: | In yeast, the protein phosphatase Cdc14 promotes chromosome segregation, mitotic exit, and cytokinesis by reversing M-phase phosphorylations catalyzed by Cdk1. A key feature of Cdc14 regulation is its sequestration within the nucleolus, which restricts its access to potential substrates for much of the cell cycle. Mammals also possess a nucleolar Cdc14 homolog, termed Cdc14B, but its roles during mitosis and cell division remain speculative. Here we analyze Cdc14B's subcellular dynamics during mitosis and rigorously test its functional contributions to cell division through homozygous disruption of the Cdc14B locus in human somatic cells. While Cdc14B is initially released from nucleoli at the start of mitosis, the phosphatase quickly redistributes onto segregating sister chromatids during anaphase. This relocalization is mainly driven by Cdk1 inactivation, as pharmacologic inhibition of Cdk1 in prometaphase cells redirects Cdc14B onto chromosomes. However, in sharp contrast to yeast cdc14 mutants, human Cdc14BΔ/Δ cells were viable and lacked defects in spindle assembly, anaphase progression, mitotic exit, and cytokinesis, and continued to segregate ribosomal DNA repeats with near-normal proficiency. Our findings reveal substantial divergence in mitotic regulation between yeast and mammalian cells, as the latter possess efficient mechanisms for completing late M-phase events in the absence of a nucleolar Cdc14-related phosphatase. ©2008 Landes Bioscience. |
| Keywords: | human cell; protein function; cell proliferation; mitosis; protein analysis; mammalia; cell cycle proteins; cell survival; cells, cultured; cell division; sister chromatid; reverse transcription polymerase chain reaction; transcription initiation; gene locus; enzyme activity; evolution, molecular; species specificity; cell strain hek293; gene disruption; enzyme inactivation; protein transport; sister chromatid exchange; anaphase; spindle cell; mitotic spindle apparatus; mitosis rate; cell cycle m phase; dna microarray; dual-specificity phosphatases; microtubule; enzyme release; dna extraction; phosphoric monoester hydrolases; rna splicing; chromosome segregation; cytokinesis; cyclin dependent kinase 1; knockout; nucleolus; yeasts; phosphoprotein phosphatase cdc14; cdc2 protein kinase; prometaphase; dna, ribosomal; ribosomal dna; ribosome dna; chromosome insertion; cell nucleolus |
| Journal Title: | Cell Cycle |
| Volume: | 7 |
| Issue: | 9 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2008-05-01 |
| Start Page: | 1184 |
| End Page: | 1190 |
| Language: | English |
| PUBMED: | 18418058 |
| PROVIDER: | scopus |
| DOI: | 10.4161/cc.7.9.5792 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 26" - "Export Date: 17 November 2011" - "Source: Scopus" |
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