Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair

Mocciaro, Annamaria; Berdougo, Eli; Zeng, Kang; Black, Elizabeth J.; Vagnarelli, Paola; Earnshaw, William C.; Gillespie, David A.; Jallepalli, Prasad V.; Schiebel, Elmar

doi:10.1083/jcb.200910057

Cited by 98 publications

(122 citation statements)

References 25 publications

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“…As in previous reports (22,25), hCDC14A was found in the cytoplasm, at centrosomes of interphase cells and at the midbody during cytokinesis (Fig. S2A).…”

Section: Resultssupporting

confidence: 64%

“…Second, the F-actin associated signal of the anti-hCDC14A antibodies was not observed in hTERT-immortalized retinal pigment epithelial (RPE1) hCDC14A KO cells (Fig. S3I) from which exon 2 had been removed to introduce a frameshift that blocked the production of hCDC14A protein (22). We note that the anti-hCDC14A antibodies detected a weak nuclear signal that may arise from the cross-reactivity with a nuclear protein in some RPE1 hCDC14A KO cells.…”

Section: Resultsmentioning

confidence: 99%

“…Schizosaccharomyces pombe Cdc14/Flp1 primarily participates in the regulation of the phosphatase Cdc25 and cytokinesis (19). Vertebrate CDC14s have been linked to diverse functions ranging from centrosome maturation and separation, DNA damage checkpoint control, DNA repair, and cytokinesis control (20)(21)(22)(23)(24). These studies have unraveled novel functions of mammalian CDC14 phosphatases; however, they reveal striking inadequacies in our understanding of this important phosphatase family.…”

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confidence: 99%

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Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

Chen

Uddin

Voit

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cell adhesion and migration are highly dynamic biological processes that play important roles in organ development and cancer metastasis. Their tight regulation by small GTPases and protein phosphorylation make interrogation of these key processes of great importance. We now show that the conserved dualspecificity phosphatase human cell-division cycle 14A (hCDC14A) associates with the actin cytoskeleton of human cells. To understand hCDC14A function at this location, we manipulated native loci to ablate hCDC14A phosphatase activity (hCDC14A PD ) in untransformed hTERT-RPE1 and colorectal cancer (HCT116) cell lines and expressed the phosphatase in HeLa FRT T-Rex cells. Ectopic expression of hCDC14A induced stress fiber formation, whereas stress fibers were diminished in hCDC14A PD cells. hCDC14A PD cells displayed faster cell migration and less adhesion than wild-type controls. hCDC14A colocalized with the hCDC14A substrate kidneyand brain-expressed protein (KIBRA) at the cell leading edge and overexpression of KIBRA was able to reverse the phenotypes of hCDC14A PD cells. Finally, we show that ablation of hCDC14A activity increased the aggressive nature of cells in an in vitro tumor formation assay. Consistently, hCDC14A is down-regulated in many tumor tissues and reduced hCDC14A expression is correlated with poorer survival of patients with cancer, to suggest that hCDC14A may directly contribute to the metastatic potential of tumors. Thus, we have uncovered an unanticipated role for hCDC14A in cell migration and adhesion that is clearly distinct from the mitotic and cytokinesis functions of Cdc14/Flp1 in budding and fission yeast.CDC14 | cell migration | cell adhesion | phosphatase

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“…As in previous reports (22,25), hCDC14A was found in the cytoplasm, at centrosomes of interphase cells and at the midbody during cytokinesis (Fig. S2A).…”

Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

Chen

Uddin

Voit

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…26 Recent data also suggest that Cdc14B seems to be necessary for efficient DNA repair. 27,28 In this study, we show that transfection of Cdc14B into normal NIH-3T3 fibroblasts leads to disruption of the F-actin cytoskeleton and cellular morphology, together with additional features of cellular transformation, such as loss of contact inhibition and ability to grow in the absence of a solid substrate. Using microarray expression profiling, we have observed a significant similarity between the gene expression profiles of Cdc14B-and H-RasV12-overexpressing cells.…”

Section: Introductionmentioning

confidence: 64%

“…Elimination of Cdc14B has been shown to be dispensable for somatic cells, although it may lead to defects in DNA repair. 27,30 We therefore tested whether Cdc14B may be required for the oncogenic activity of H-RasV12 by knocking down Cdc14B expression in H-RasV12 transformed cells. We transfected the NIH3T3 H-Ras stable clones with two series of plasmids (pA90 and pPRIME, see Materials and Methods) that codify different shRNA interfering for Cdc14B expression.…”

confidence: 99%

The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway

Chiesa¹,

Guillamot²,

Bueno³

et al. 2011

Cell Cycle

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Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

2019

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Here, we will review the evidence showing that mitotic exit is initiated by regulated proteolysis and then driven by the PPP family of phosphoserine/threonine phosphatases. Rapid APC/CCDC20 and ubiquitin‐dependent proteolysis of cyclin B and securin initiates sister chromatid separation, the first step of mitotic exit. Because proteolysis of Aurora and Polo family kinases dependent on APC/CCDH1 is relatively slow, this creates a new regulatory state, anaphase, different to G2 and M‐phase. We will discuss how the CDK1‐counteracting phosphatases PP1 and PP2A‐B55, together with Aurora and Polo kinases, contribute to the temporal regulation and order of events in the different stages of mitotic exit from anaphase to cytokinesis. For PP2A‐B55, these timing properties are created by the ENSA‐dependent inhibitory pathway and differential recognition of phosphoserine and phosphothreonine. Finally, we will discuss how Aurora B and PP2A‐B56 are needed for the spatial regulation of anaphase spindle formation and how APC/C‐dependent destruction of PLK1 acts as a timer for abscission, the final event of cytokinesis.

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Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair

Abstract: Cdc14A and Cdc14B knockout cells with double-strand breaks still arrest in G2, but they fail to repair the damage.

Cited by 98 publications

References 25 publications

Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion

The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway

Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

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