Phosphorylation Mediated Regulation of Cdc25 Activity, Localization and Stability

Frazer, Corey; Young, Paul G.

doi:10.5772/48315

Cited by 9 publications

(19 citation statements)

References 303 publications

(406 reference statements)

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“…CDC25A overexpression accelerates the entry into the DNA replication phase by dephosphorylation of CDK2/cyclin E, which additionally phosphorylates Rb [25] and mutually activates CDC25A in a feed-forward loop [21,29]. CDC25A reaches its highest expression level at late G1-phase, where it together with CDC25B facilitates the transition into S-phase by dephosphorylation of CDK2/cyclin A, which in turn activates DNA replicating proteins [30]. CDC25C controls the initiation of the S-phase [31].…”

Section: Figurementioning

confidence: 99%

“…CDC25C controls the initiation of the S-phase [31]. At late S-phase, CDC25B dephosphorylates CDK1/cyclin A, a less active complex compared to CDK2/cyclin A, which persists throughout G2-phase [30]. Dephosphorylation of CDK1/cyclin B by CDC25 is the rate-limiting step for the G2 to mitosis transition [32].…”

Section: Figurementioning

confidence: 99%

“…CDC25B is most abundant and active at late G2-phase and during mitosis, and is localized to the centrosome where it dephosphorylates CDK1/cyclin B [35,36]. The latter is subsequently translocated to the nucleus, where it is completely activated by CDC25C leading to mitotic onset [30]. CBC25B is then phosphorylated and this is supposed to be important for the regulation of the mitotic entry [37].…”

Section: Figurementioning

confidence: 99%

“…Two other important kinases positively regulate CDC25s and promote mitosis: the polo-like kinase 1 (PLK1) and Aurora kinases. The former activates CDC25C both directly and indirectly by CDK1/cyclin B phosphorylation and inhibition of the Wee1-like kinase Myt1 [44], in addition to favoring the nuclear import of CDC25C [30,45], whereas the latter activates both PLK1 and CDC25s [46,47]. PLK1 also plays a role in mitotic exit, as it is a positive regulator of the APC/C activity [48].…”

Section: Control Of Cdc25 Expression and Activitymentioning

confidence: 99%

“…At the G1/S checkpoint, DNA synthesis is inhibited, whereas intra-S phase arrest blocks mitotic entry until the S-phase is completed [30]. Finally, at the G2/M checkpoint, damaged cells are arrested in order to allow for cell repair or apoptosis [49].…”

Section: Cell Cycle Arrest and Cdc25 Inhibitionmentioning

confidence: 99%

See 4 more Smart Citations

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

et al. 2014

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Abstract:The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs). CDC25s seem to have a role in the development of several human malignancies, including acute myeloid leukemia (AML); and CDC25 inhibition is therefore considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can enhance cell proliferation and the expression seems to be controlled through PI3K-Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML. Loss of CDC25A is also important for the cell cycle arrest caused by differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B expression is associated with resistance against the antiproliferative effect of PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this isoform seems to reduce AML cell line proliferation through effects on NFκB and p300. Finally, CDC25C seems important for the phenotype of AML cells at least for a subset of patients. Many of the identified CDC25 inhibitors show cross-reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive inhibitors it may become possible to inhibit OPEN ACCESSMolecules 2014, 19 18415 several molecular events in the regulation of cell cycle progression and even cytoplasmic signaling, including activation of several CDKs, through the use of a single drug. Such combined strategies will probably be an advantage in human cancer treatment.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Control Of Cdc25 Expression and Activitymentioning

confidence: 99%

Section: Cell Cycle Arrest and Cdc25 Inhibitionmentioning

confidence: 99%

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Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

et al. 2014

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Link of Zygotic Genome Activation and Cell Cycle Control

Liu

Großhans

2017

Methods in Molecular Biology

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The activation of the zygotic genome and onset of transcription in blastula embryos is linked to changes in cell behavior and remodeling of the cell cycle and constitutes a transition from exclusive maternal to zygotic control of development. This step in development is referred to as mid-blastula transition and has served as a paradigm for the link between developmental program and cell behavior and morphology. Here, we discuss the mechanism and functional relationships between the zygotic genome activation and cell cycle control during mid-blastula transition with a focus on Drosophila embryos.

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Phosphorylation of CDC25A on SER283 in late S/G2 by CDK/cyclin complexes accelerates mitotic entry

et al. 2016

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The Cdc25A phosphatase is an essential activator of CDK-cyclin complexes at all steps of the eukaryotic cell cycle. The activity of Cdc25A is itself regulated in part by positive and negative feedback regulatory loops performed by its CDK-cyclin substrates that occur in G1 as well as during the G1/S and G2/M transitions. However, the regulation of Cdc25A during G2 phase progression before mitotic entry has not been intensively characterized. Here, we identify by mass spectrometry analysis a new phosphorylation event of Cdc25A on Serine283. Phospho-specific antibodies revealed that the phosphorylation of this residue appears in late S/G2 phase of an unperturbed cell cycle and is performed by CDK-cyclin complexes. Overexpression studies of wild-type and non-phosphorylatable mutant forms of Cdc25A indicated that Ser283 phosphorylation increases the G2/M-promoting activity of the phosphatase without impacting its stability or subcellular localization. Our results therefore identify a new positive regulatory loop between Cdc25A and its CDK-cyclin substrates which contributes to accelerate entry into mitosis through the regulation of Cdc25A activity in G2.

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Phosphorylation Mediated Regulation of Cdc25 Activity, Localization and Stability

Cited by 9 publications

References 303 publications

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

Link of Zygotic Genome Activation and Cell Cycle Control

Phosphorylation of CDC25A on SER283 in late S/G2 by CDK/cyclin complexes accelerates mitotic entry

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