Disease relevance of CDC25C

• CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form [1].
• Our objective was to evaluate the expression of the three cell cycle-related phosphatases CDC25A, CDC25B and CDC25C in patients with ovarian cancer [2].
• G2 arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes [3].
• Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells [4].

High impact information on CDC25C

• Here we show that the catalytic activity of human cdc25-C phosphatase is also activated directly by phosphorylation in mitotic cells [5].
• Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis [5].
• Cells arrested in G2 phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species [3].
• Temozolomide-treated cells induced to overexpress Akt, however, exhibited significantly less drug-induced Cdc25C/Cdc2 inactivation and less G2 arrest [6].
• Our results show that whereas CDC25C is expressed at a low level with no relevant differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are overexpressed in a large fraction of tumors [7].

Chemical compound and disease context of CDC25C

• Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells [8].

Biological context of CDC25C

• CDK2 activity was suppressed by caffeine, whereas activity of CDC2 was enhanced by suppressing phosphorylation on Tyr15 and by interfering with 14-3-3 binding to CDC25C [9].
• Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C [10].
• This residue is equivalent to serine 216 in human CDC25C which plays an important role in the regulation of phosphatase during the cell cycle and at the G2 checkpoint. pEg3 is also able to specifically associate with CDC25B in vitro and in vivo [11].
• The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P < 0.05) [12].
• We have localized CDC25C and WEE1 respectively at 5q31 and 11p15.3-11p15.1 using fluorescent in situ hybridization of cDNA probes on human chromosomes [13].

Anatomical context of CDC25C

• To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines [1].
• The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation [14].
• A Polo-like kinase 1 (Plk1) appears involved in an autocatalytic loop between CDC25C phosphatase and M phase promoting factor (MPF) in Xenopus oocytes and leads to activation of MPF that is required for germinal vesicle breakdown (GVBD) [15].
• Radiation with 1 Gy prevents the activation of the mitotic inducers mitosis-promoting factor (MPF) and cdc25-C in HeLa cells [16].
• We recently demonstrated that cdc2 expression is associated with the biological aggressiveness of malignant lymphoma of the thyroid [17].

Associations of CDC25C with chemical compounds

• In contrast, p34cdc2 in U937-ASPI3K maintained in an active state by dephosphorylation on threonine 14 (Thr 14) and tyrosine 15 (Tyr 15), which was associated with constant nuclear CDC25A, CDC25B and CDC25C protein abundance before and after irradiation [18].
• Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their benzimidazole-indazole- or isoindole-dione counterparts [19].
• Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C [20].
• Furthermore, the activity of cdc25-C phosphatase was decreased after treatment of cells with C2 toxin [4].
• In addition, the decline in the expression of Cdc25C was completely blocked when the cells were treated with lactacystin (proteasome inhibitor) prior to BITC treatment [21].

Enzymatic interactions of CDC25C

• For its activation at the G2/M border, p34cdc2 needs to be associated with cyclin B and additionally dephosphorylated at Tyr-15 by the specific phosphatase cdc25-C [4].
• The basic mechanism of this assay is to observe the phosphorylated levels of a fragment of CDC25C containing the site that can be phosphorylated by CHK1 in vitro [22].

Regulatory relationships of CDC25C

• Thus, interaction between 14-3-3 proteins and CDC25B is regulated in a manner that is different from that with CDC25C [23].
• In marked contrast, CHK2 expressed in either mammalian cells or in bacteria is already active as a kinase against itself and CDC25C and can delay cell cycle progression [24].
• Since C2 toxin delayed entry into mitosis in HeLa cells, those enzymes which control entry into mitosis, the cyclin-dependent protein kinase mitosis-promoting factor (MPF) and the phosphatase cdc25-C were examined after treatment of synchronized cells with C2 toxin [4].
• Upon omega-3 fatty acids treatment, cyclin B1 phosphorylation was inhibited and the expression of the cell division cycle 25C phosphatase, which dephosphorylates cyclin-dependent kinase 1, was decreased [25].
• Furthermore, expression of CDC25C alone inactivated the DNA synthesis control whereas p53 and CDC25C coexpressing yeast cells showed an intact checkpoint control [26].

Other interactions of CDC25C

• Western blot was employed to measure nuclear protein abundance of CDC25A, CDC25B, CDC25C, total p34cdc2, p34cdc2, (Thr 161) or p34cdc2 (Thr 14, Tyr 15) [18].
• Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer [1].
• However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant [27].
• This p14(ARF)-induced G(2) arrest was correlated with inhibition of CDC2 activity, inactivation of CDC25C phosphatase and induction of the CDK inhibitor p21(WAFI) [28].
• Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively [29].

Analytical, diagnostic and therapeutic context of CDC25C

• Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15.1 by fluorescence in situ hybridization [13].
• Immunoprecipitation data showed 14-3-3zeta could bind to CDC25C in irradiated A549 cells, and suppression of 14-3-3zeta in A549 cells with antisense resulted in a decrease in CDC25C localization in cytoplasm and CDC2 phosphorylation on Tyr15 [30].
• CDC25A, CDC25B and CDC25C expression were investigated by immunohistochemistry in 106 patients with ovarian cancer [2].
• We have overexpressed and purified human dual-specificity phosphatase cdc25C from a prokaryotic expression system at high levels and in a soluble, active form, and have studied and quantified its potential to interact with cdks, cyclins and preformed cdk-cyclin complexes by fluorescence spectroscopy and size-exclusion chromatography [31].

References