Aurora B Regulates Formin mDia3 in Achieving Metaphase Chromosome Alignment

Cheng, Lina; Zhang, Jiayin; Ahmad, Sana; Rozier, Lorène; Yu, Hang; Deng, Haiteng; Mao, Yinghui

doi:10.1016/j.devcel.2011.01.008

Cited by 93 publications

(119 citation statements)

References 43 publications

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“…One possibility is that hCDC14A dephosphorylates actin modulators such as the guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that regulate the activity of actin controlling small GTPases. Indeed, components of Rho GTPase pathways such as the nucleotide exchange factor GEF-H1, MyoGEF, RacGAP, and mDia3 are phosphorylated by the mitotic kinases CDK1, Polo kinase 1, and Aurora kinases (48)(49)(50)(51)(52). Because hCDC14A is a proline-directed phosphatase (31), it is plausible that it counteracts a proline-directed kinase such as CDK1.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…This release allows the FH2 domain to nucleate actin (Schonichen and Geyer, 2010;Wallar et al, 2006). All apicomplexan parasites lack these regulatory domains, but there is abundant literature covering studies in mammals and yeast that highlight how phosphorylation regulates formins activity (Cheng et al, 2011;Iskratsch et al, 2010;Wang et al, 2009). In this context it is intriguing and likely relevant to notice the large cluster of phosphorylation sites on the C-terminal region of TgFRM2.…”

Section: Actin Dynamicsmentioning

confidence: 99%

Does protein phosphorylation govern host cell entry and egress by the Apicomplexa?

Jacot

Soldati‐Favre

2012

International Journal of Medical Microbiology

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a b s t r a c tMembers of the phylum Apicomplexa are responsible for a wide range of diseases in humans and animals. The absence of an effective vaccine or safe curing drugs and the continuous emergence of resistant parasites to available treatments impose a high demand on the identification of novel targets for intervention against the apicomplexans. Protein kinases are considered attractive potential therapeutic targets not only against cancers but also to combat infectious diseases. The scope and aim of this review is to report on the recent progress in dissecting the impact of protein phosphorylation in regulating motility and invasion.

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“…1). While investigating kinetochore functions of formin mDia3 28,29 using quantitative imaging, we have unexpectedly observed that depleting mDia2, but not mDia3, results in an almost 50% reduction of total CENP-A levels at centromeres after one round of cell cycle. 30 Furthermore, ratiometric live cell imaging studies (Fig.…”

Section: A Rho Family Small Gtpase Molecular Switch Is Required For Nmentioning

confidence: 99%

Formin-mediated epigenetic maintenance of centromere identity

Liu

Mao

2016

Small GTPases

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Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres. A constitutively active mDia2 construct is able to rescue the CENP-A loading defect caused by MgcRacGAP depletion. This study has uncovered an unsuspected role of the cytoskeleton protein mDia2 as an effector of the MgcRacGAP-dependent small GTPase signaling inside the nucleus to participate in the epigenetic regulation of centromere maintenance during cell cycle.

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Aurora B Regulates Formin mDia3 in Achieving Metaphase Chromosome Alignment

Cited by 93 publications

References 43 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

Does protein phosphorylation govern host cell entry and egress by the Apicomplexa?

Formin-mediated epigenetic maintenance of centromere identity

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