Antisense phosphorothioate oligonucleotides specifically down-regulate cdc25B causing S-phase delay and persistent antiproliferative effects

Garner-Hamrick, Peggy A.; Fisher, Chris

doi:10.1002/(sici)1097-0215(19980529)76:5<720::aid-ijc18>3.0.co;2-7

Cited by 53 publications

(35 citation statements)

References 40 publications

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“…In support of this idea, a cell cycle-dependent transport of Cdc25B in and out of the nucleus, has been demonstrated in somatic cells (Girard et al, 1992;Garner-Hamrick and Fisher, 1998;Dalal et al, 1999;Davezac et al, 2000) and in mouse oocytes (Solc et al, 2008). Our immunocytochemical experiments revealed a restricted cytoplasmic localization of Cdc25B in G 2 -arrested oocytes and nuclear localization shortly before GVBD.…”

Section: Discussionsupporting

confidence: 83%

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

Zhang

et al. 2008

Developmental Dynamics

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Protein kinase A (PKA) play a critical role in maintaining the meiotic arrest. However, the steps downstream of PKA remain largely unknown. In this study, we investigated the regulation of meiotic resumption by PKA/Cdc25B pathway in mouse oocytes. Injection of mRNA coding for Cdc25b-S321A had a more potent maturation-inducing ability than Cdc25b-WT. When co-injected with PKA inhibitor, Cdc25B-WT had similar activities with Cdc25B-S321A. Meanwhile, the phosphorylation of Cdc25B-S321 was detected in germinal vesicle (GV) oocytes by Western blotting with a phospho-Ser321-specific antibody and the band disappeared when oocytes reenter into the meiotic cell cycle. Furthermore, Cdc25B-WT translocated to the nucleus shortly before GV breakdown (GVBD), whereas phosphorylated Cdc25B-S321 expressed exclusively in the cytoplasm and the signal could not be detected in GVBD oocytes. Taken together, these data indicate that Cdc25B-Serine321 is the potential PKA target and Cdc25B subcellular localization determines its function during the process of maintaining GV arrest in mouse oocytes. Developmental Dynamics 237: 3777-3786, 2008.

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Section: Discussionsupporting

confidence: 83%

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

Zhang

et al. 2008

Developmental Dynamics

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“…Inhibition of CDC25A activity in HeLa cells using antibodies which inhibited cell division, resulted in the accumulation of cells with mitotic-like phenotype and death (Galaktionov and Beach, 1991). Inhibition of CDC25B using antisense approach lead to delay in S phase with subsequent antiproliferative effects (Garner-Hamrick and Fisher, 1998). Based on this information, the CDC25 family has been the subject of a screen for inhibitory compounds.…”

Section: Cdc25mentioning

confidence: 99%

Targeting the cell cycle for cancer therapy

Carnero

2002

Br J Cancer

140

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Most if not all neoplasias show a directly or indirectly deregulated cell cycle. Targeting its regulatory molecules, the cyclindependent kinases, as a therapeutic mode to develop new anticancer drugs, is being currently explored in both academia and pharmaceutical companies. The development of new compounds is being focused on the many features of the cell cycle with promising preclinical data in most fields. Moreover, a few compounds have entered clinical trials with excellent results maintaining the high hopes. Thus, although too early to provide a cell cycle target based new commercial drug, there is no doubt that it will be an excellent source of new anticancer compounds.

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“…The precise role of CDC25B is less clear. Its phosphatase activity is detectable from S phase to mitosis, and controversial sets of results suggest a role for CDC25B in the progression into S phase (Garner-Hamrick and Fisher, 1998), in G2 phase or at the G2/M transition (Gabrielli et al, 1996;Lammer et al, 1998;Karlsson et al, 1999). This apparent controversy may reflect the existence of subpopulations of CDC25B, which act at different stages of the cell cycle, in specific subcellular compartments.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase CK2 regulates CDC25B phosphatase activity

et al. 2003

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Human dual-specificity phosphatases CDC25 (A, B and C) play an important role in the control of cell cycle progression by activating the cyclin-dependent kinases (CDKs). Regulation of these phosphatases during the cell cycle involves post-translational modifications such as phosphorylation and protein-protein interactions. Given the suspected involvement of the protein kinase CK2 at the G2/M transition, we have investigated its effects on the CDC25B phosphatase. We show that in vitro CK2 phosphorylates CDC25B, but not CDC25C. Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. We also report that CDC25B interacts with CK2, and this interaction, mediated by the CK2b regulatory subunit, involves domains that are located within the first 55 amino acids of CK2b and between amino acids 122 and 200 on CDC25B. This association was confirmed in vivo, in Sf9 insect cells and in U 2 OS human cells expressing an HA epitope-tagged CDC25B. Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. We discuss the possibility that CDC25B phosphorylation by CK2 could play a role in the regulation of the activity of CDC25B as a starter of mitosis.

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Antisense phosphorothioate oligonucleotides specifically down-regulate cdc25B causing S-phase delay and persistent antiproliferative effects

Cited by 53 publications

References 40 publications

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

Protein kinase a modulates Cdc25B activity during meiotic resumption of mouse oocytes

Targeting the cell cycle for cancer therapy

Protein kinase CK2 regulates CDC25B phosphatase activity

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