CDC25A

Summary

Gene Symbol: CDC25A
Description: cell division cycle 25A
Alias: CDC25A2, M-phase inducer phosphatase 1, CDC25 isoform A1-CAG, CDC25A2-CAG isoform, dual specificity phosphatase CDC25A
Species: human
Products:     CDC25A

Top Publications

  1. Zou X, Tsutsui T, Ray D, Blomquist J, Ichijo H, Ucker D, et al. The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001;21:4818-28 pubmed
    b>CDC25A phosphatase promotes cell cycle progression by activating G(1) cyclin-dependent kinases and has been postulated to be an oncogene because of its ability to cooperate with RAS to transform rodent fibroblasts...
  2. Xu X, Burke S. Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25. J Biol Chem. 1996;271:5118-24 pubmed
    ..In this study, the catalytic mechanism and substrate binding specificity of human Cdc25A and -B proteins were investigated by site-directed and deletion mutagenesis methods...
  3. Blomberg I, Hoffmann I. Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases. Mol Cell Biol. 1999;19:6183-94 pubmed
    ..In the present study, we have investigated the function of human Cdc25A phosphatase. Cell lines that express human Cdc25A in an inducible manner have been generated...
  4. Vigo E, Muller H, Prosperini E, Hateboer G, Cartwright P, Moroni M, et al. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol Cell Biol. 1999;19:6379-95 pubmed
    ..Furthermore, CDC25A is defined as a novel E2F target whose expression can be directly regulated by E2F-1...
  5. Nilsson I, Hoffmann I. Cell cycle regulation by the Cdc25 phosphatase family. Prog Cell Cycle Res. 2000;4:107-14 pubmed
    ..in higher eukaryotic cells can be achieved through dephosphorylation by members of the Cdc25 phosphatase family, Cdc25A, Cdc25B and Cdc25C. Cdc25A plays an important role at the G1/S-phase transition...
  6. Mailand N, Falck J, Lukas C, Syljuasen R, Welcker M, Bartek J, et al. Rapid destruction of human Cdc25A in response to DNA damage. Science. 2000;288:1425-9 pubmed
    ..to ultraviolet light or ionizing radiation by rapid, ubiquitin- and proteasome-dependent protein degradation of Cdc25A, a phosphatase that is required for progression from G1 to S phase of the cell cycle...
  7. Falck J, Mailand N, Syljuasen R, Bartek J, Lukas J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature. 2001;410:842-7 pubmed
    ..The Cdc25A phosphatase activates the cyclin-dependent kinase 2 (Cdk2) needed for DNA synthesis, but becomes degraded in ..
  8. McCain D, Catrina I, Hengge A, Zhang Z. The catalytic mechanism of Cdc25A phosphatase. J Biol Chem. 2002;277:11190-200 pubmed
    ..catalytic mechanism of Cdc25, we have performed a detailed mechanistic analysis of the catalytic domain of human Cdc25A. Our kinetic isotope effect results, Bronsted analysis, and pH dependence studies employing a range of aryl ..
  9. Wang Z, Wang M, Lazo J, Carr B. Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase. J Biol Chem. 2002;277:19470-5 pubmed
    b>Cdc25A, a dual-specificity protein phosphatase, plays a critical role in cell cycle progression. Although cyclin-dependent kinases are established substrates, Cdc25A may also affect other proteins...

More Information

Publications107 found, 100 shown here

  1. Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta G. Dual mode of degradation of Cdc25 A phosphatase. EMBO J. 2002;21:4875-84 pubmed
    ..We propose that a dual mechanism of regulated degradation allows for fine tuning of Cdc25 A abundance in response to cell environment. ..
  2. Chen M, Ryan C, Piwnica Worms H. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol. 2003;23:7488-97 pubmed
    The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk1 kinase-Cdc25A phosphatase pathway...
  3. Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge S, et al. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003;17:3062-74 pubmed
    ..A central target of the cell cycle arrest program is the Cdc25A protein phosphatase...
  4. Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta G. Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle. 2004;3:469-71 pubmed
    We have recently demonstrated that regulation of Cdc25A protein abundance during S phase and in response to DNA damage is mediated by SCF(betaTrCP) activity...
  5. Esteban V, Vázquez Novelle M, Calvo E, Bueno A, Sacristán M. Human Cdc14A reverses CDK1 phosphorylation of Cdc25A on serines 115 and 320. Cell Cycle. 2006;5:2894-8 pubmed
    ..Here, we show that human Cdc14A can dephosphorylate Cdc25A in vitro...
  6. Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung M, et al. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell. 2008;13:36-47 pubmed publisher
    The Cdc25A phosphatase positively regulates cell-cycle transitions, is degraded by the proteosome throughout interphase and in response to stress, and is overproduced in human cancers...
  7. Ray D, Kiyokawa H. CDC25A phosphatase: a rate-limiting oncogene that determines genomic stability. Cancer Res. 2008;68:1251-3 pubmed publisher
    b>CDC25A is a critical regulator of cell cycle progression and checkpoint response. Overexpression of this cyclin-dependent kinase phosphatase occurs often in human cancers...
  8. Jin J, Ang X, Ye X, Livingstone M, Harper J. Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase. J Biol Chem. 2008;283:19322-8 pubmed publisher
    ..cells activate a signaling pathway that promotes cell cycle arrest and degradation of the cell cycle regulator Cdc25A. Cdc25A degradation occurs via the SCFbeta-TRCP pathway and phosphorylation of Ser-76...
  9. Mailand N, Podtelejnikov A, Groth A, Mann M, Bartek J, Lukas J. Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO J. 2002;21:5911-20 pubmed
    DNA replication in higher eukaryotes requires activation of a Cdk2 kinase by Cdc25A, a labile phosphatase subject to further destabilization upon genotoxic stress...
  10. Hassepass I, Voit R, Hoffmann I. Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint. J Biol Chem. 2003;278:29824-9 pubmed
    The human Cdc25A phosphatase plays a pivotal role at the G1/S transition by activating cyclin E and A/Cdk2 complexes through dephosphorylation. In response to ionizing radiation, Cdc25A is phosphorylated by both Chk1 and Chk2 on Ser-123...
  11. Goloudina A, Yamaguchi H, Chervyakova D, Appella E, Fornace A, Bulavin D. Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. Cell Cycle. 2003;2:473-8 pubmed
    Degradation of Cdc25A phosphatase is an ubiquitous feature of stress. There are some discrepancies in the reported roles for different phosphorylation sites in the regulation of Cdc25A stability...
  12. Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello N, et al. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 2003;426:87-91 pubmed
    The Cdc25A phosphatase is essential for cell-cycle progression because of its function in dephosphorylating cyclin-dependent kinases...
  13. Ray D, Terao Y, Nimbalkar D, Chu L, Donzelli M, Tsutsui T, et al. Transforming growth factor beta facilitates beta-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner. Mol Cell Biol. 2005;25:3338-47 pubmed
    Ubiquitin-dependent degradation of Cdc25A is a major mechanism for damage-induced S-phase checkpoint...
  14. Alchab F, Sibille E, Ettouati L, Bana E, Bouaziz Z, Mularoni A, et al. Screening of indeno[1,2-b]indoloquinones by MALDI-MS: a new set of potential CDC25 phosphatase inhibitors brought to light. J Enzyme Inhib Med Chem. 2016;31:25-32 pubmed
    ..Biological investigations showed that only compounds 5c-f inhibited CDC25A and -C phosphatases, with IC50 values around the micromolar range...
  15. Lin C, Lee M, Lin J, Lin M, Chueh F, Yu C, et al. Crude extract of Rheum palmatum L. Induces cell cycle arrest S phase and apoptosis through mitochondrial-dependent pathways in U-2 OS human osteosarcoma cells. Environ Toxicol. 2016;31:957-69 pubmed publisher
    ..PARP, GRP78, GADD153, AIF, Endo G, Calpain-2, p21, and p27, but decreased the levels of Bcl-2, BCL-X, XIAP, Akt, CDC25A, CDK2, Cyclin A, and Cyclin E of U-2 OS cells...
  16. Yang S, Huang A, Tang N, Liu H, Liao C, Ji B, et al. Bisdemethoxycurcumin-induced S phase arrest through the inhibition of cyclin A and E and induction of apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathways in human lung cancer NCI H460 cells. Environ Toxicol. 2016;31:1899-1908 pubmed publisher
    ..Western blotting results showed that BDMC inhibited Cdc25A, cyclin A and E for causing S phase arrest, furthermore, promoted the expression of AIF, Endo G and PARP and the ..
  17. Lee J, Kim I, Nam T. Crude extract and solvent fractions of Calystegia soldanella induce G1 and S phase arrest of the cell cycle in HepG2 cells. Int J Oncol. 2017;50:414-420 pubmed publisher
    ..fraction treatment also arrested HepG2 cells in the S phase, with decreased expression of cyclin A, CDK2, and CDC25A. Also, treatment with this fraction reduced the expression of retinoblastoma (RB) protein and the transcription ..
  18. Pal H, Katiyar S. Cryptolepine, a Plant Alkaloid, Inhibits the Growth of Non-Melanoma Skin Cancer Cells through Inhibition of Topoisomerase and Induction of DNA Damage. Molecules. 2016;21: pubmed publisher
    ..g., Cdc25a and Cdc25b) leading to cell cycle arrest at S-phase; and (iv) mitochondrial membrane potential was disrupted and ..
  19. Yang H, Wu L, Ke S, Wang W, Yang L, Gao X, et al. Downregulation of Ubiquitin-conjugating Enzyme UBE2D3 Promotes Telomere Maintenance and Radioresistance of Eca-109 Human Esophageal Carcinoma Cells. J Cancer. 2016;7:1152-62 pubmed publisher
    ..G1-S phase transition and prolonged IR-induced G2/M arrest through over expression of cyclin D1, decrease of CDC25A expression and promotion of the ATM/ATR-Chk1-CDC25C pathway...
  20. Agustriawan D, Huang C, Sheu J, Lee S, Tsai J, Kurubanjerdjit N, et al. DNA methylation-regulated microRNA pathways in ovarian serous cystadenocarcinoma: A meta-analysis. Comput Biol Chem. 2016;65:154-164 pubmed publisher
    ..We also found that several miRNA target genes, BTG3, NDN, HTRA3, CDC25A, and HMGA2 were also related to the poor outcomes in ovarian cancer...
  21. Wen H, Chuu C, Chen C, Shiah S, Kung H, King K, et al. Elevation of soluble guanylate cyclase suppresses proliferation and survival of human breast cancer cells. PLoS ONE. 2015;10:e0125518 pubmed publisher
    ..Elevation of sGC reduced protein abundance of Bcl-2, Bcl-xL, Cdc2, Cdc25A, Cyclin B1, Cyclin D1, Cdk6, c-Myc, and Skp2 while increased protein expression of p53...
  22. da Silveira J, Winger Q, Bouma G, Carnevale E. Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare. Reprod Fertil Dev. 2015;27:897-905 pubmed publisher
    ..DNA-binding protein inhibitor ID-2 (ID2), signal transducer and activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A). Finally, changes in exosomal miRNA predicted to target selected TGF-β members were identified.
  23. Lv M, Li Y, Tian X, Dai S, Sun J, Jin G, et al. Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and metastasis. Drug Des Devel Ther. 2016;10:3737-3746 pubmed
    ..Moreover, knockdown of NLK led to cell cycle arrest at the S-phase via suppression of Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition...
  24. Wu F, Su S, Tan G, Yan L, Li T, Zhang H, et al. Mus81 knockdown sensitizes colon cancer cells to chemotherapeutic drugs by activating CHK1 pathway. Clin Res Hepatol Gastroenterol. 2017;41:592-601 pubmed publisher
    ..knockdown also induced S phase arrest and elevated apoptosis in CDDP treated HCT116 cells through activating CHK1/CDC25A/CDK2 and CHK1/p53/Bax pathways, while these effects could be counteracted by CHK1 inhibition...
  25. Ben Younes K, Body S, Costé Ã, Viailly P, Miloudi H, Coudre C, et al. A lowered 26S proteasome activity correlates with mantle lymphoma cell lines resistance to genotoxic stress. BMC Cancer. 2017;17:538 pubmed publisher
    ..We observed that three main actors of apoptosis, senescence and cell cycle regulation (cyclin D1, MCL1 and CDC25A) failed to be degraded by the proteasome machinery in REC1 cells...
  26. Kim C, Lee H, Gupta N, Ramachandran S, Kaushik I, Srivastava S, et al. Role of Forkhead Box Class O proteins in cancer progression and metastasis. Semin Cancer Biol. 2018;50:142-151 pubmed publisher
    ..the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-..
  27. Xie X, Xu Z, Wang C, Fang C, Zhao J, Xu L, et al. Tip60 is associated with resistance to X-ray irradiation in prostate cancer. FEBS Open Bio. 2018;8:271-278 pubmed publisher
    ..by inducing apoptosis, reduced the acetylation of ATM and decreased the expression of phosphorylated ATM, Chk2 and cdc25A in both DU145 and LNCaP cells after X-ray irradiation...
  28. Li M, Lu J, Zhang F, Li H, Zhang B, Wu X, et al. Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway. Cancer Lett. 2014;355:201-9 pubmed publisher
    ..inhibited cell proliferation by inducing cell cycle arrest in S phase in concordance with the decrease of CDK2, CDC25A, and cyclin A, and resulted in increased cell apoptosis and invasive repression in GBC cell lines in vitro...
  29. Cizkova K, Steigerova J, Gursky J, Ehrmann J. Stimulating effect of normal-dosing of fibrates on cell proliferation: word of warning. Lipids Health Dis. 2016;15:164 pubmed
    ..is accompanyed by elevation of CYP2J2, increased number of cyclin E-positive cells and decreased number of Cdc25A-positive cells in all tested cell lines, and elevated cyclin A expression in HepG2 and HT-29...
  30. Cen W, Feng Y, Li S, Huang W, Zhang T, Zhang W, et al. Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells. J Cell Physiol. 2017;: pubmed publisher
    ..The levels of p-p38 and p53 were up-regulated while those of cdc25A and p-ERK 1/2 were down-regulated. Phosphorylation of Stat3 and its downstream proteins was all decreased...
  31. Takamochi K, Mogushi K, Kawaji H, Imashimizu K, Fukui M, Oh S, et al. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma. PLoS ONE. 2017;12:e0175622 pubmed publisher
    ..glucose metabolism (GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1, CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although expression levels were lower in EGFR-mutated than in wild-type ..
  32. Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E. Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest. Mol Cell Biol. 1999;19:1460-9 pubmed
    ..Our results suggest that cyclin E may modulate the activity of the SWI-SNF apparatus to maintain the chromatin in a transcriptionally permissive state. ..
  33. Brisson M, Foster C, Wipf P, Joo B, Tomko R, Nguyen T, et al. Independent mechanistic inhibition of cdc25 phosphatases by a natural product caulibugulone. Mol Pharmacol. 2007;71:184-92 pubmed
    ..Caulibugulone A also caused the selective degradation of Cdc25A protein by a process that was independent of reactive oxygen species production, proteasome activity, and the Chk1 ..
  34. Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed S, et al. Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest. Mol Cell Biol. 1996;16:3934-44 pubmed
    ..The latter resulted from the rapid alpha-interferon-mediated elimination of cdc25A, a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk2 in cyclin-cdk ..
  35. Luczak M, Zhitkovich A. Nickel-induced HIF-1? promotes growth arrest and senescence in normal human cells but lacks toxic effects in transformed cells. Toxicol Appl Pharmacol. 2017;331:94-100 pubmed publisher
    ..increased levels of MYC protein but did not change protein expression of the cell cycle-promoting phosphatase CDC25A or the CDK inhibitor p16...
  36. Zhao H, Watkins J, Piwnica Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A. 2002;99:14795-800 pubmed
    ..In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR...
  37. Huang M, Wang J, Chang H, Kuo C, Tok T, Lin S. CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer. Oncol Rep. 2011;25:1297-306 pubmed publisher
    ..In 110 CRC tissues, we detected five genes CDC25A, VAV1, TP73, BRCA1 and ZAP70 from 15 overexpressed genes that significantly related to prognostic factors (tumor ..
  38. Wu Y, Kang T. Protein stability regulators screening assay (Pro-SRSA): protein degradation meets the CRISPR-Cas9 library. Chin J Cancer. 2016;35:60 pubmed publisher
    ..article entitled "A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A," recently published in Cell Discovery, our team developed a protein stability regulators screening assay (Pro-..
  39. Peschiaroli A, Skaar J, Pagano M, Melino G. The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene. 2010;29:1384-93 pubmed publisher
    ..Notably, genetic or siRNA-mediated depletion of USP47 induced accumulation of Cdc25A, decreased cell survival and augmented the cytotoxic effects of anticancer drugs...
  40. Hong H, Choi J, Cho Y, Kim B. Cdc25A promotes cell survival by stimulating NF-?B activity through I?B-? phosphorylation and destabilization. Biochem Biophys Res Commun. 2012;420:293-6 pubmed publisher
    Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized...
  41. Iavarone A, Massague J. E2F and histone deacetylase mediate transforming growth factor beta repression of cdc25A during keratinocyte cell cycle arrest. Mol Cell Biol. 1999;19:916-22 pubmed
    b>cdc25A is a tyrosine phosphatase that activates G1 cyclin-dependent kinases (Cdk's)...
  42. Yu Y, Xing K, Badamas R, Kuszynski C, Wu H, Lou M. Overexpression of thioredoxin-binding protein 2 increases oxidation sensitivity and apoptosis in human lens epithelial cells. Free Radic Biol Med. 2013;57:92-104 pubmed publisher
    ..arrested at the G2/M stage and that they displayed low expression of the cell cycle elements P-cdc2(Y15), cdc2, cdc25A, and cdc25C. Furthermore, TBP-2 OE cells were more sensitive to oxidation...
  43. Liu P, Barkley L, Day T, Bi X, Slater D, Alexandrow M, et al. The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism. J Biol Chem. 2006;281:30631-44 pubmed
    ..Chk1-dependent inhibition of DNA synthesis in BPDE-treated cells occurred without detectable changes in Cdc25A levels, Cdk2 activity, or Cdc7/Dbf4 interaction...
  44. Hammer S, To K, Yoo Y, Koshiji M, Huang L. Hypoxic suppression of the cell cycle gene CDC25A in tumor cells. Cell Cycle. 2007;6:1919-26 pubmed
    ..of the hypoxic effects on cell cycle in tumor cells, here we report that hypoxia inhibits the expression of CDC25A, another cell cycle gene encoding a tyrosine phosphatase that maintains CDK2 activity...
  45. Sørensen C, Syljuåsen R, Falck J, Schroeder T, Ronnstrand L, Khanna K, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell. 2003;3:247-58 pubmed
    ..that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A, and caused radioresistant DNA ..
  46. Myer D, Robbins S, Yin M, Boivin G, Liu Y, Greis K, et al. Absence of polo-like kinase 3 in mice stabilizes Cdc25A after DNA damage but is not sufficient to produce tumors. Mutat Res. 2011;714:1-10 pubmed publisher
    ..Here we show that Plk3 phosphorylates the key cell cycle protein phosphatase Cdc25A on two serine residues in its cyclinB/cdk1 docking domain and regulates its stability in response to DNA damage...
  47. Ding X, Husseman J, Tomashevski A, Nochlin D, Jin L, Vincent I. The cell cycle Cdc25A tyrosine phosphatase is activated in degenerating postmitotic neurons in Alzheimer's disease. Am J Pathol. 2000;157:1983-90 pubmed
    ..To explain this atypical mitotic activation in neurons we investigated the Cdc2-activating Cdc25A phosphatase in human brain...
  48. Goto H, Izawa I, Li P, Inagaki M. Novel regulation of checkpoint kinase 1: Is checkpoint kinase 1 a good candidate for anti-cancer therapy?. Cancer Sci. 2012;103:1195-200 pubmed publisher
    ..In this review, we summarize recent advances in Chk1 regulation by phosphorylation, and discuss Chk1 as a molecular target for cancer therapeutics. ..
  49. Brenner A, Reikvam H, Lavecchia A, Bruserud Ø. 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. Molecules. 2014;19:18414-47 pubmed publisher
    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)...
  50. Källström H, Lindqvist A, Pospisil V, Lundgren A, Rosenthal C. Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import. Exp Cell Res. 2005;303:89-100 pubmed
    ..b>Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle...
  51. Demidova A, Aau M, Zhuang L, Yu Q. Dual regulation of Cdc25A by Chk1 and p53-ATF3 in DNA replication checkpoint control. J Biol Chem. 2009;284:4132-9 pubmed publisher
    ..It is well known that ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is a crucial mechanism conferring this checkpoint activation...
  52. Maiti G, Mondal P, Mukherjee N, Ghosh A, Ghosh S, Dey S, et al. Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and CDC25A genes. PLoS ONE. 2013;8:e63440 pubmed publisher
    ..In addition, deletion/methylation/mutation/expression of SH3GL2 (associated with EGFR degradation) and CDC25A (associated with dephosphorylation of EGFR) were analyzed in the same set of samples...
  53. Liu Y, Sepich D, Solnica Krezel L. Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation. PLoS Genet. 2017;13:e1006564 pubmed publisher
    ..Stat3 regulates cell proliferation and axis extension in part via upregulation of Cdc25a expression during oogenesis...
  54. Wang Y, Compton C, Rankin G, Cutler S, Rojanasakul Y, Tu Y, et al. 3-Hydroxyterphenyllin, a natural fungal metabolite, induces apoptosis and S phase arrest in human ovarian carcinoma cells. Int J Oncol. 2017;50:1392-1402 pubmed publisher
    ..Downregulation of cyclin D1, cyclin A2, cyclin E1, CDK2, CDK4 and Cdc25C, and the upregulation of Cdc25A and cyclin B1 led to the accumulation of cells in S phase...
  55. Wang L, Liu L, Wang J, Chen Y. Inhibitory Effect of Artesunate on Growth and Apoptosis of Gastric Cancer Cells. Arch Med Res. 2017;48:623-630 pubmed publisher
    ..Flow cytometry was used to detect the CDC25A protein expression in different gastric diseases...
  56. Li Y, Ji S, Fu L, Jiang T, Wu D, Meng F. Knockdown of Cyclin-Dependent Kinase Inhibitor 3 Inhibits Proliferation and Invasion in Human Gastric Cancer Cells. Oncol Res. 2017;25:721-731 pubmed publisher
    ..marker expression showed that CDKN3 knockdown promotes cell cycle arrest by decreasing the expression of CDK2, CDC25A, CCNB1, and CCNB2 in human gastric cancer cells...
  57. Lu Y, Li F, Xu T, Sun J. miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A. Oncol Res. 2016;23:155-63 pubmed publisher
    ..By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells...
  58. Gao D, Inuzuka H, Tan M, Fukushima H, Locasale J, Liu P, et al. mTOR drives its own activation via SCF(?TrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell. 2011;44:290-303 pubmed publisher
  59. Tan H, Gao S, Zhuang Y, Dong Y, Guan W, Zhang K, et al. R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase. Mar Drugs. 2016;14: pubmed publisher
    ..CyclinA, CDK2 and CDC25A are proteins associated with the S phase, and it was found that R-PE could increase the expression of cyclin A ..
  60. Strausfeld U, Labbe J, Fesquet D, Cavadore J, Picard A, Sadhu K, et al. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature. 1991;351:242-5 pubmed
    ..We propose that the cdc25+ gene product directly activates the p34cdc2-cyclin B complex. ..
  61. Coqueret O, Bérubé G, Nepveu A. The mammalian Cut homeodomain protein functions as a cell-cycle-dependent transcriptional repressor which downmodulates p21WAF1/CIP1/SDI1 in S phase. EMBO J. 1998;17:4680-94 pubmed
    ..was shown to result both from an increase in Cut expression and dephosphorylation of the Cut homeodomain by the Cdc25A phosphatase. We also show that the increase in Cut activity coincides with a decrease in p21WAF1/CIP1/SDI1 mRNAs...
  62. Qu Z, Weiss J, MacLellan W. Regulation of the mammalian cell cycle: a model of the G1-to-S transition. Am J Physiol Cell Physiol. 2003;284:C349-64 pubmed
    ..which includes the interactions between cyclin E (CycE), cyclin-dependent kinase 2 (CDK2), and protein phosphatase CDC25A, exhibits dynamics such as limit cycle, bistability, and excitable transient...
  63. Lin Y, Chung C, Cheng Y. Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis. J Clin Endocrinol Metab. 2009;94:2650-7 pubmed publisher
    Human BOLL is known as a meiotic regulator, and CDC25A is considered as a potential RNA target of BOLL...
  64. Wang Y, Sun H, Xiao Z, Zhang D, Bao X, Wei N. XWL-1-48 exerts antitumor activity via targeting topoisomerase II and enhancing degradation of Mdm2 in human hepatocellular carcinoma. Sci Rep. 2017;7:9989 pubmed publisher
    ..and p-ATM expression, and further triggered DNA damage response through activation of ATM-p53-p21 and ATM-Chk2-Cdc25A pathways. Targeted inhibition of ATM by siRNA attenuated the ability of XWL-1-48 on inducing DNA damage...
  65. Doerr F, George J, Schmitt A, Beleggia F, Rehkämper T, Hermann S, et al. Targeting a non-oncogene addiction to the ATR/CHK1 axis for the treatment of small cell lung cancer. Sci Rep. 2017;7:15511 pubmed publisher
    ..In line with uncontrolled cell cycle progression in SCLC, we find that CDC25A, B and C mRNAs are expressed at significantly higher levels in SCLC, compared to lung adenocarcinoma...
  66. Conklin D, Galaktionov K, Beach D. 14-3-3 proteins associate with cdc25 phosphatases. Proc Natl Acad Sci U S A. 1995;92:7892-6 pubmed
    ..family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases...
  67. Galaktionov K, Lee A, Eckstein J, Draetta G, Meckler J, Loda M, et al. CDC25 phosphatases as potential human oncogenes. Science. 1995;269:1575-7 pubmed
    ..In human cells, CDC25 proteins are encoded by a multigene family, consisting of CDC25A, CDC25B, and CDC25C...
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    b>Cdc25A regulates cell cycle progression, has oncogenic and anti-apoptotic activity, and is over-expressed in many human tumors. Phosphorylation by Chk1 and Cds1/Chk2 down-regulates Cdc25A levels in response to genotoxic stresses...
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    ..The mitotic DNA damage responses were independent of p53 and pRb, but they were dependent on ATM. CDC25A that accumulated during mitosis was rapidly destroyed after DNA damage in an ATM-dependent manner...
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    Current evidence suggests that CDC25A is not only a major regulator of both G(1)/S and G(2)/M transition during unperturbed cell cycle progression, but also a critical checkpoint mediator...
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    ..We report here that CDC25A, a cell cycle-promoting phosphatase over-expressed in a number of cancers, functions as an AR coregulator ..
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    ..Genes encoding FAS and cell cycle proteins such as CDC25A contain Sp1 binding sites in their promoters...
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    ..The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator...
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    The dual specificity (Tyr/Thr) phosphatase Cdc25A activates cyclin-dependent kinases (Cdks) to promote cell-cycle progression and has significant oncogenic potential...
  75. Sakai S, Ohoka N, Onozaki K, Kitagawa M, Nakanishi M, Hayashi H. Dual mode of regulation of cell division cycle 25 A protein by TRB3. Biol Pharm Bull. 2010;33:1112-6 pubmed
    ..Here we demonstrate that TRB3 regulates the stability of cell division cycle 25 A (Cdc25A), an essential activator of cyclin dependent kinases (CDKs)...
  76. Yun H, Hyun S, Park J, Kim B, Kwon H. Widdrol activates DNA damage checkpoint through the signaling Chk2-p53-Cdc25A-p21-MCM4 pathway in HT29 cells. Mol Cell Biochem. 2012;363:281-9 pubmed publisher
    ..with widdrol elicits the following: (1) phosphorylation of Chk2 and p53, (2) reduction of cell division cycle 25A (Cdc25A) expression, (3) increase of Cdk inhibitor p21 expression, and (4) decrease of the levels of Cdk2 and cyclin E ..
  77. Brunetto E, Ferrara A, Rampoldi F, Talarico A, Cin E, Grassini G, et al. CDC25A protein stability represents a previously unrecognized target of HER2 signaling in human breast cancer: implication for a potential clinical relevance in trastuzumab treatment. Neoplasia. 2013;15:579-90 pubmed
    The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2) in mammary epithelial cells...
  78. Fukasawa T, Enomoto A, Miyagawa K. Serine-Threonine Kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint. Cell Signal. 2015;27:1569-75 pubmed publisher
    ..A key regulator of cell-cycle arrest is the CDC25A (cell division cycle 25 homologue A) phosphatase...
  79. Bertoli S, Boutzen H, David L, Larrue C, Vergez F, Fernandez Vidal A, et al. CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia. Oncotarget. 2015;6:38061-78 pubmed publisher
    ..Upon FLT3 inhibition, CDC25A mRNA and protein were rapidly down-regulated, while levels of other cell cycle proteins remained unchanged...
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    Two previously unidentified human cdc25 genes have been isolated, cdc25A and cdc25B. Both genes rescue a cdc25ts mutant of fission yeast. Microinjection of anti-cdc25A antibodies into HeLa cells causes their arrest in mitosis...
  81. Fauman E, Cogswell J, Lovejoy B, Rocque W, Holmes W, Montana V, et al. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998;93:617-25 pubmed
    Cdc25 phosphatases activate the cell division kinases throughout the cell cycle. The 2.3 A structure of the human Cdc25A catalytic domain reveals a small alpha/beta domain with a fold unlike previously described phosphatase structures but ..
  82. Sexl V, Diehl J, Sherr C, Ashmun R, Beach D, Roussel M. A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2. Oncogene. 1999;18:573-82 pubmed
    The cdc25A phosphatase removes inhibitory phosphates from threonine-14 and tyrosine-15 of cyclin dependent kinase-2 (cdk2) in vitro, and it is therefore widely assumed that cdc25A positively regulates cyclin E- and A-associated cdk2 ..
  83. Lee J, Collins K, Brown A, Lee C, Chung J. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature. 2000;404:201-4 pubmed
    ..Phosphorylation of BRCA1 at serine 988 is required for the release of BRCA1 from hCds1. This phosphorylation is also important for the ability of BRCA1 to restore survival after DNA damage in the BRCA1-mutated cell line HCC1937. ..
  84. Wegener S, Hampe W, Herrmann D, Schaller H. Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C. Eur J Cell Biol. 2000;79:810-5 pubmed
    ..We identified four new splice variants in the amino-terminal regulatory region of human cdc25C and one in cdc25A. All variants except one retain an intact catalytic domain...
  85. Wang Z, Southwick E, Wang M, Kar S, Rosi K, Wilcox C, et al. Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs. Cancer Res. 2001;61:7211-6 pubmed
    ..In this study, we show that Cdc25A, a protein phosphatase, was inactivated by novel arylating K vitamin analogues...
  86. Nguyen D, Westbrook T, McCance D. Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol. 2002;76:619-32 pubmed
    ..Most pathways that govern cell growth converge on downstream effectors. Among these is the cdc25A tyrosine phosphatase...
  87. Xu X, Yamamoto H, Sakon M, Yasui M, Ngan C, Fukunaga H, et al. Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas. Clin Cancer Res. 2003;9:1764-72 pubmed
    ..CDC25 genes are cell cycle-activating phosphatases that positively regulate the activity of cyclin-dependent kinase. CDC25A and CDC25B, being oncogenes, are overexpressed in a variety of human malignancies...
  88. Mondesert O, Lemaire M, Brezak M, Galera Contour M, Prevost G, Ducommun B, et al. A fission yeast strain expressing human CDC25A phosphatase: a tool for selectivity studies of pharmacological inhibitors of CDC25. Curr Genet. 2004;45:283-8 pubmed
    ..We examined by homologous recombination whether the human CDC25A phosphatase could substitute for the function of the fission yeast Cdc25. We first show: (a)...
  89. Ito Y, Yoshida H, Matsuzuka F, Matsuura N, Nakamura Y, Nakamine H, et al. Cdc25A and cdc25B expression in malignant lymphoma of the thyroid: correlation with histological subtypes and cell proliferation. Int J Mol Med. 2004;13:431-5 pubmed
    Cdc25B and cdc25A phosphatases are representative stimulators of cell cycle progression, and recent studies have also indicated their oncogenic roles...
  90. Rother K, Kirschner R, Sanger K, Böhlig L, MOssner J, Engeland K. p53 downregulates expression of the G1/S cell cycle phosphatase Cdc25A. Oncogene. 2007;26:1949-53 pubmed
    Overexpression of Cdc25A phosphatase is often observed in cancer and results in poor prognosis...
  91. Lehmann G, McCabe M. Arsenite slows S phase progression via inhibition of cdc25A dual specificity phosphatase gene transcription. Toxicol Sci. 2007;99:70-8 pubmed
    ..b>Cdc25A dual specificity phosphatase controls entry into and progression through S phase by dephosphorylating sites of ..
  92. Tomko R, Lazo J. Multimodal control of Cdc25A by nitrosative stress. Cancer Res. 2008;68:7457-65 pubmed publisher
    b>Cdc25A propels cell cycle progression, is overexpressed in numerous human cancers, and possesses oncogenic and antiapoptotic activities...