An additional transcript of the cdc25C gene from A431 cells encodes a functional protein.

Bureik, Matthias; Rief, Nicole; Drescher, Rudolf; Jungbluth, Andreas; Montenarh, Mathias; Wagner, P.

doi:10.3892/ijo.17.6.1251

Cited by 15 publications

(24 citation statements)

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“…In addition to the full-length CDC25C protein examined above, there are alternatively spliced of CDC25C transcripts that have been detected in a number of cancer cell lines (18,19). The immunoglobulin heavy chain that is present in large amounts in some patient samples may interfere with direct measurement of the alternatively spliced proteins in clinical samples.…”

Section: Resultsmentioning

confidence: 99%

“…This alternatively spliced transcript has a deletion of exons 3, 5, and 6 of the CDC25C gene and encodes a smaller protein containing the COOH-terminal catalytic domain and 17 unique amino acids. This alternatively spliced variant can complement a CDC25C mutant strain of Schizosaccharomyces pombe (19). It is interesting to note that this variant leads to an increased uncoupling of the onset of mitosis and the completion of DNA synthesis in this mutant strain of S. pombe, implying poor regulation of the activity of this variant protein.…”

Section: Discussionmentioning

confidence: 99%

“…RNAs extracted from the prostate tissues were first reverse transcribed as previously described (21) and analyzed for the presence of two different cDNAs for CDC25C using the following primers flanking the deletions of the CDC25C sequence: forward, 5V -AGAGAGAAGCTTATGTCTACG-GAACTCTTCTCATCC-3V ; reverse, 5V -CCCAAATATTTCATTTCACTGTCC3Vas described previously by Bureik et al (19). The h-actin primers were as described previously (22).…”

Section: Methodsmentioning

confidence: 99%

“…Activated Chk kinases can phosphorylate CDC25C at Ser 216 , blocking the activation of Cdc2 and transition into the M phase (16). Another aspect of CDC25 regulation is alternative splicing that may produce at least five CDC25B variants (17), and splice variants are also reported for CDC25A and CDC25C (18,19). The activity and regulation of CDC25C in prostate carcinoma has not been previously examined, despite its potentially important role in the G 2 -M transition in this common malignancy.…”

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confidence: 99%

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Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Özen

Ittmann

2005

Clinical Cancer Research

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Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G 2 -M transition by activating Cdc2/Cyclin B1 complexes. 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. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. 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. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease.Abnormal expression and/or activity of cell cycle regulatory proteins have been identified in a wide variety of malignant neoplasms, including prostate cancer. Cell cycle progression is controlled by the sequential activities of cyclin-dependent kinases, whose activities are tightly regulated by cyclins, cyclin-dependent kinase inhibitors, and a variety of other proteins. Several groups have shown increased expression of cyclin B1, which plays a critical role in the G 2 -M transition, in human prostate cancers (1, 2). Recent work by Maddison et al. (3) has shown increased levels of cyclin B1 in poorly differentiated and androgen-independent prostate cancers in the TRAMP mouse model of prostate cancer. During G 2 , the Cdc2/Cyclin B complex is kept inactive by phosphorylation of Cdc2 by Wee1. At the onset of mitosis, Cdc2/Cyclin B complexes are dephosphorylated by CDC25 phosphatase leading to increased kinase activity (4 -6). Our laboratory has shown previously that disruption of fibroblast growth factor signaling in prostate cancer cells leads to decrease in Cdc2 kinase activity and arrest in G 2 followed by cell death (7). These findings imply that the G 2 -M transition may be a critical checkpoint in prostate cancer.CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. In human cells, CDC25 proteins are encoded by a multigene fa...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Özen

Ittmann

2005

Clinical Cancer Research

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“…Among these phosphatases is a family of highly conserved proteins of the cdc25 family namely cdc25A, cdc25B and cdc25C expressed in mammalian cells (3). For each family member, there is a number of known different splice variants (4)(5)(6). Each member of the cdc25 family has different functions during the cell cycle by dephosphorylating specific substrates.…”

Section: Introductionmentioning

confidence: 99%

Interference between p53 and cdc25C in cell cycle regulation

Ruppenthal

Noll²,

Götz³

et al. 2007

Int J Oncol

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Abstract. The eukaryotic cell cycle is regulated by a network of different protein kinases and phosphatases which are by various mechanisms linked to the growth suppressor p53. Cell cycle regulation is quite similar from yeast to man. Although there is no endogenous p53 in yeast expression of human p53 led to growth arrest of yeast cells which can be suppressed by simultaneous overexpression of cdc25C, a phosphatase regulating entry into mitosis. Herein, we show that overexpression of cdc25C in mammalian cells is insufficient in suppressing a p53 induced growth arrest. We further show that p53 is co-immunoprecipitated with cdc25C and p53 inhibits the cdc25C phosphatase activity in a dose-dependent manner. Thus, our data show that p53 like other binding partners of cdc25C, regulates entry into mitosis by binding to cdc25C.

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Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies

2016

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Alterations in the cell cycle regulatory genes result in uncontrolled cell proliferation leading to several disease conditions. Cyclin-dependent kinases (CDK) and their regulatory subunit, cyclins, are essential proteins in cell-cycle progression. The activity of CDK is regulated by a series of phosphorylation and dephosphorylation at different amino acid residues. Cell Division Cycle-25 (CDC25) plays an important role in transitions between cell cycle phases by dephosphorylating and activating CDKs. CDC25B and CDC25C play a major role in G2/M progression, whereas CDC25A assists in G1/S transition. Different isomers of CDC25 expressions are upregulated in various clinicopathological situations. Overexpression of CDC25A deregulates G1/S and G2/M events, including the G2 checkpoint. CDC25B has oncogenic properties. Binding to the 14-3-3 proteins regulates the activity and localization of CDC25B. CDC25C is predominantly a nuclear protein in mammalian cells. At the G2/M transition, mitotic activation of CDC25C protein occurs by its dissociation from 14-3-3 proteins along with its phosphorylation at multiple sites within its N-terminal domain. In this article, we critically reviewed the biology of the activation/deactivation of CDC25 by kinases/phosphatases to maintain the level of CDK–cyclin activities and thus the genomic stability, clinical implications due to dysregulation of CDC25 and potential role of CDC25 inhibitors in diseases.

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An additional transcript of the cdc25C gene from A431 cells encodes a functional protein.

Cited by 15 publications

References 0 publications

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer

Interference between p53 and cdc25C in cell cycle regulation

Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies

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