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Abstract:

Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Registro:

Documento: Artículo
Título:Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
Autor:Giono, L.E.; Resnick-Silverman, L.; Carvajal, L.A.; St Clair, S.; Manfredi, J.J.
Filiación:Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología Biología Molecular y Celular and CONICET-Universidad de Buenos Aires, Instituto de Fisiología Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United States
Department of Oncological Sciences and Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Palabras clave:Cdc25C protein; proteasome; protein MDM2; protein p53; protein tyrosine phosphatase; small interfering RNA; ubiquitin protein ligase; unclassified drug; antineoplastic antibiotic; doxorubicin; MDM2 protein, human; protein MDM2; protein p53; protein tyrosine phosphatase; animal cell; Article; Cdc25C gene; controlled study; DNA damage; down regulation; embryo; enzyme metabolism; enzyme stability; G2 phase cell cycle checkpoint; gene amplification; gene expression regulation; gene interaction; gene knockdown; gene overexpression; gene repression; human; Mdm2 gene; mouse; nonhuman; oncogene; priority journal; promoter region; protein degradation; protein expression; protein function; protein protein interaction; protein targeting; transcription regulation; tumor suppressor gene; ubiquitination; animal; cell culture; cell line; drug effects; G2 phase cell cycle checkpoint; genetics; HCT 116 cell line; immunoblotting; knockout mouse; metabolism; protein degradation; RNA interference; tumor cell line; Animals; Antibiotics, Antineoplastic; cdc25 Phosphatases; Cell Line; Cell Line, Tumor; Cells, Cultured; Down-Regulation; Doxorubicin; G2 Phase Cell Cycle Checkpoints; Gene Expression Regulation; HCT116 Cells; Humans; Immunoblotting; Mice, Knockout; Proteolysis; Proto-Oncogene Proteins c-mdm2; RNA Interference; Tumor Suppressor Protein p53
Año:2017
Volumen:36
Número:49
Página de inicio:6762
Página de fin:6773
DOI: http://dx.doi.org/10.1038/onc.2017.254
Título revista:Oncogene
Título revista abreviado:Oncogene
ISSN:09509232
CODEN:ONCNE
CAS:proteasome, 140879-24-9; protein tyrosine phosphatase, 79747-53-8, 97162-86-2; receptor type tyrosine protein phosphatase C; ubiquitin protein ligase, 134549-57-8; doxorubicin, 23214-92-8, 25316-40-9; Antibiotics, Antineoplastic; cdc25 Phosphatases; Doxorubicin; MDM2 protein, human; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v36_n49_p6762_Giono

Referencias:

  • Vousden, K.H., Lu, X., Live or let die: The cell's response to p53 (2002) Nat Rev Cancer, 2, pp. 594-604
  • Donehower, L.A., Harvey, M., Slagle, B.L., McArthur, M.J., Montgomery, C.A., Jr., Butel, J.S., Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours (1992) Nature, 356, pp. 215-221
  • Vogelstein, B., Lane, D., Levine, A.J., Surfing the p53 network (2000) Nature, 408, pp. 307-310
  • Kubbutat, M.H., Jones, S.N., Vousden, K.H., Regulation of p53 stability by Mdm2 (1997) Nature, 387, pp. 299-303
  • Oliner, J.D., Pietenpol, J.A., Thiagalingam, S., Gyuris, J., Kinzler, K.W., Vogelstein, B., Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53 (1993) Nature, 362, pp. 857-860
  • Shvarts, A., Steegenga, W.T., Riteco, N., Van Laar, T., Dekker, P., Bazuine, M., MDMX: A novel p53-binding protein with some functional properties of MDM2 (1996) Embo J, 15, pp. 5349-5357
  • Jones, S.N., Roe, A.E., Donehower, L.A., Bradley, A., Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53 (1995) Nature, 378, pp. 206-208
  • Migliorini, D., Denchi, E.L., Danovi, D., Jochemsen, A., Capillo, M., Gobbi, A., Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development (2002) Mol Cell Biol, 22, pp. 5527-5538
  • Montes De Oca Luna, R., Wagner, D.S., Lozano, G., Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53 (1995) Nature, 378, pp. 203-206
  • Oliner, J.D., Kinzler, K.W., Meltzer, P.S., George, D.L., Vogelstein, B., Amplification of a gene encoding a p53-associated protein in human sarcomas (1992) Nature, 358, pp. 80-83
  • Manfredi, J.J., The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor (2010) Genes Dev, 24, pp. 1580-1589
  • Brown, D.R., Thomas, C.A., Deb, S.P., The human oncoprotein MDM2 arrests the cell cycle: Elimination of its cell-cycle-inhibitory function induces tumorigenesis (1998) Embo J, 17, pp. 2513-2525
  • Dang, J., Kuo, M.L., Eischen, C.M., Stepanova, L., Sherr, C.J., Roussel, M.F., The RING domain of Mdm2 can inhibit cell proliferation (2002) Cancer Res, 62, pp. 1222-1230
  • Folberg-Blum, A., Sapir, A., Shilo, B.Z., Oren, M., Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila (2002) Oncogene, 21, pp. 2413-2417
  • Lundgren, K., Montes De Oca Luna, R., McNeill, Y.B., Emerick, E.P., Spencer, B., Barfield, C.R., Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53 (1997) Genes Dev, 11, pp. 714-725
  • Ohkubo, S., Tanaka, T., Taya, Y., Kitazato, K., Prives, C., Excess HDM2 impacts cell cycle and apoptosis and has a selective effect on p53 dependent transcription (2006) J Biol Chem, 281, pp. 16943-16950
  • Zhou, R., Frum, R., Deb, S., Deb, S.P., The growth arrest function of the human oncoprotein mouse double minute-2 is disabled by downstream mutation in cancer cells (2005) Cancer Res, 65, pp. 1839-1848
  • Piwnica-Worms, H., Cell cycle. Fools rush in (1999) Nature, 401, p. 537
  • Imbriano, C., Gurtner, A., Cocchiarella, F., Di Agostino, S., Basile, V., Gostissa, M., Direct p53 Transcriptional Repression: In Vivo Analysis of CCAAT-Containing G2/M Promoters (2005) Mol Cell Biol, 25, pp. 3737-3751
  • Le Gac, G., Esteve, P.O., Ferec, C., Pradhan, S., DNA damage-induced down-regulation of human Cdc25C and Cdc2 is mediated by cooperation between p53 and maintenance DNA (Cytosine-5) methyltransferase 1 (2006) J Biol Chem, 281, pp. 24161-24170
  • Lohr, K., Moritz, C., Contente, A., Dobbelstein, M., P21/CDKN1A Mediates Negative Regulation of Transcription by p53 (2003) J Biol Chem, 278, pp. 32507-32516
  • Manni, I., Mazzaro, G., Gurtner, A., Mantovani, R., Haugwitz, U., Krause, K., NF-Y mediates the transcriptional inhibition of the cyclin B1, cyclin B2, and cdc25C promoters upon induced G2 arrest (2001) J Biol Chem, 276, pp. 5570-5576
  • St Clair, S., Giono, L., Varmeh-Ziaie, S., Resnick-Silverman, L., Liu, W.J., Padi, A., DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: One involves direct binding to the cdc25C promoter (2004) Mol Cell, 16, pp. 725-736
  • Badie, C., Itzhaki, J.E., Sullivan, M.J., Carpenter, A.J., Porter, A.C., Repression of CDK1 and other genes with CDE and CHR promoter elements during DNA damage-induced G(2)/M arrest in human cells (2000) Mol Cell Biol, 20, pp. 2358-2366
  • St Clair, S., Manfredi, J.J., The dual specificity phosphatase Cdc25C is a direct target for transcriptional repression by the tumor suppressor p53 (2006) Cell Cycle, 5, pp. 709-713
  • Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 (2004) Science, 303, pp. 844-848
  • Giono, L.E., Manfredi, J.J., Mdm2 is required for inhibition of Cdk2 activity by p21, thereby contributing to p53-dependent cell cycle arrest (2007) Mol Cell Biol, 27, pp. 4166-4178
  • Pines, J., Hunter, T., Isolation of a human cyclin cDNA: Evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2 (1989) Cell, 58, pp. 833-846
  • Innocente, S.A., Abrahamson, J.L., Cogswell, J.P., Lee, J.M., P53 regulates a G2 check-point through cyclin B1 (1999) Proc Natl Acad Sci USA, 96, pp. 2147-2152
  • Jin, Y., Lee, H., Zeng, S.X., Dai, M.S., Lu, H., MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation (2003) Embo J, 22, pp. 6365-6377
  • Singh, S.V., Herman-Antosiewicz, A., Singh, A.V., Lew, K.L., Srivastava, S.K., Kamath, R., Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C (2004) J Biol Chem, 279, pp. 25813-25822
  • Xu, H., Zhang, Z., Li, M., Zhang, R., MDM2 promotes proteasomal degradation of p21Waf1 via a conformation change (2010) J Biol Chem, 285, pp. 18407-18414
  • Chin, L., Pomerantz, J., Depinho, R.A., The INK4a/ARF tumor suppressor: One gene-two products--two pathways (1998) Trends Biochem Sci, 23, pp. 291-296
  • Zhang, Y., Xiong, Y., Yarbrough, W.G., ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways (1998) Cell, 92, pp. 725-734
  • Fang, S., Jensen, J.P., Ludwig, R.L., Vousden, K.H., Weissman, A.M., Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 (2000) J Biol Chem, 275, pp. 8945-8951
  • Honda, R., Tanaka, H., Yasuda, H., Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53 (1997) FEBS Lett, 420, pp. 25-27
  • Peng, C.Y., Graves, P.R., Thoma, R.S., Wu, Z., Shaw, A.S., Piwnica-Worms, H., Mitotic and G2 checkpoint control: Regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216 (1997) Science, 277, pp. 1501-1505
  • Graves, P.R., Lovly, C.M., Uy, G.L., Piwnica-Worms, H., Localization of human Cdc25C is regulated both by nuclear export and 14-3-3 protein binding (2001) Oncogene, 20, pp. 1839-1851
  • Turowski, P., Franckhauser, C., Morris, M.C., Vaglio, P., Fernandez, A., Lamb, N.J., Functional cdc25C dual-specificity phosphatase is required for S-phase entry in human cells (2003) Mol Biol Cell, 14, pp. 2984-2998
  • Chen, F., Zhang, Z., Bower, J., Lu, Y., Leonard, S.S., Ding, M., Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway (2002) Proc Natl Acad Sci USA, 99, pp. 1990-1995
  • Xiao, D., Johnson, C.S., Trump, D.L., Singh, S.V., 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 (2004) Mol Cancer Ther, 3, pp. 567-575
  • Vecchione, A., Baldassarre, G., Ishii, H., Nicoloso, M.S., Belletti, B., Petrocca, F., Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development (2007) Cancer Cell, 11, pp. 275-289
  • Sdek, P., Ying, H., Chang, D.L., Qiu, W., Zheng, H., Touitou, R., MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein (2005) Mol Cell, 20, pp. 699-708
  • Chowdary, D.R., Dermody, J.J., Jha, K.K., Ozer, H.L., Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway (1994) Mol Cell Biol, 14, pp. 1997-2003
  • Asher, G., Lotem, J., Sachs, L., Kahana, C., Shaul, Y., Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1 (2002) Proc Natl Acad Sci USA, 99, pp. 13125-13130
  • Bendjennat, M., Boulaire, J., Jascur, T., Brickner, H., Barbier, V., Sarasin, A., UV irradiation triggers ubiquitin-dependent degradation of p21(WAF1) to promote DNA repair (2003) Cell, 114, pp. 599-610
  • Chen, X., Chi, Y., Bloecher, A., Aebersold, R., Clurman, B.E., Roberts, J.M., N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1) (2004) Mol Cell, 16, pp. 839-847
  • Kong, X., Lin, Z., Liang, D., Fath, D., Sang, N., Caro, J., Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha (2006) Mol Cell Biol, 26, pp. 2019-2028
  • Kawai, H., Wiederschain, D., Kitao, H., Stuart, J., Tsai, K.K., Yuan, Z.M., DNA damage-induced MDMX degradation is mediated by MDM2 (2003) J Biol Chem, 278, pp. 45946-45953
  • Donzelli, M., Draetta, G.F., Regulating mammalian checkpoints through Cdc25 inactivation (2003) EMBO Rep, 4, pp. 671-677
  • Mailand, N., Falck, J., Lukas, C., Syljuasen, R.G., Welcker, M., Bartek, J., Rapid destruction of human Cdc25A in response to DNA damage (2000) Science, 288, pp. 1425-1429
  • Wang, X., McGowan, C.H., Zhao, M., He, L., Downey, J.S., Fearns, C., Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest (2000) Mol Cell Biol, 20, pp. 4543-4552
  • Graves, P.R., Yu, L., Schwarz, J.K., Gales, J., Sausville, E.A., O'connor, P.M., The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01 (2000) J Biol Chem, 275, pp. 5600-5605
  • Liu, T.T., Liu, Y.J., Wang, Q., Yang, X.G., Wang, K., Reactive-oxygen-species-mediated Cdc25C degradation results in differential antiproliferative activities of vanadate, tungstate, and molybdate in the PC-3 human prostate cancer cell line (2012) J Biol Inorg Chem, 17, pp. 311-320
  • Raj, K., Ogston, P., Beard, P., Virus-mediated killing of cells that lack p53 activity (2001) Nature, 412, pp. 914-917
  • Eymin, B., Claverie, P., Salon, C., Brambilla, C., Brambilla, E., Gazzeri, S., P14ARF triggers G2 arrest through ERK-mediated Cdc25C phosphorylation, ubiquitination and proteasomal degradation (2006) Cell Cycle, 5, pp. 759-765
  • Thanasoula, M., Escandell, J.M., Suwaki, N., Tarsounas, M., ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres (2012) Embo J, 31, pp. 3398-3410
  • Shabbeer, S., Omer, D., Berneman, D., Weitzman, O., Alpaugh, A., Pietraszkiewicz, A., BRCA1 targets G2/M cell cycle proteins for ubiquitination and proteasomal degradation (2013) Oncogene, 32, pp. 5005-5016
  • Yan, Y., Spieker, R.S., Kim, M., Stoeger, S.M., Cowan, K.H., BRCA1-mediated G2/M cell cycle arrest requires ERK1/2 kinase activation (2005) Oncogene, 24, pp. 3285-3296
  • Burri, N., Shaw, P., Bouzourene, H., Sordat, I., Sordat, B., Gillet, M., Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer (2001) Lab Invest, 81, pp. 217-229
  • Stott, F.J., Bates, S., James, M.C., McConnell, B.B., Starborg, M., Brookes, S., The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2 (1998) Embo J, 17, pp. 5001-5014
  • Boyd, M.T., Vlatkovic, N., Haines, D.S., A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is suppressed by MDM2 (2000) J Biol Chem, 275, pp. 31883-31890
  • Ciznadija, D., Zhu, X.H., Koff, A., Hdm2-and proteasome-dependent turnover limits p21 accumulation during S phase (2011) Cell Cycle, 10, pp. 2714-2723
  • Loughran, O., La Thangue, N.B., Apoptotic and growth-promoting activity of E2F modulated by MDM2 (2000) Mol Cell Biol, 20, pp. 2186-2197
  • Uchida, C., Miwa, S., Kitagawa, K., Hattori, T., Isobe, T., Otani, S., Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation (2005) Embo J, 24, pp. 160-169
  • Wang, B., Liu, K., Lin, H.Y., Bellam, N., Ling, S., Lin, W.C., 14-3-3Tau regulates ubiquitin-independent proteasomal degradation of p21, a novel mechanism of p21 downregulation in breast cancer (2010) Mol Cell Biol, 30, pp. 1508-1527
  • Zhang, Z., Wang, H., Li, M., Agrawal, S., Chen, X., Zhang, R., MDM2 is a negative regulator of p21WAF1/CIP1, independent of p53 (2004) J Biol Chem, 279, pp. 16000-16006
  • Evans, S.C., Viswanathan, M., Grier, J.D., Narayana, M., El-Naggar, A.K., Lozano, G., An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2 (2001) Oncogene, 20, pp. 4041-4049
  • Perry, M.E., Mendrysa, S.M., Saucedo, L.J., Tannous, P., Holubar, M., P76(MDM2) inhibits the ability of p90(MDM2) to destabilize p53 (2000) J Biol Chem, 275, pp. 5733-5738
  • Calabro, V., Mansueto, G., Parisi, T., Vivo, M., Calogero, R.A., La Mantia, G., The human MDM2 oncoprotein increases the transcriptional activity and the protein level of the p53 homolog p63 (2002) J Biol Chem, 277, pp. 2674-2681
  • Kadakia, M., Slader, C., Berberich, S.J., Regulation of p63 function by Mdm2 and MdmX (2001) DNA Cell Biol, 20, pp. 321-330
  • Little, N.A., Jochemsen, A.G., Hdmx and Mdm2 can repress transcription activation by p53 but not by p63 (2001) Oncogene, 20, pp. 4576-4580
  • Ongkeko, W.M., Wang, X.Q., Siu, W.Y., Lau, A.W., Yamashita, K., Harris, A.L., MDM2 and MDMX bind and stabilize the p53-related protein p73 (1999) Curr Biol, 9, pp. 829-832
  • Girnita, L., Girnita, A., Larsson, O., Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor (2003) Proc Natl Acad Sci USA, 100, pp. 8247-8252
  • Pan, Y., Chen, J., MDM2 promotes ubiquitination and degradation of MDMX (2003) Mol Cell Biol, 23, pp. 5113-5121
  • Coutts, A.S., Boulahbel, H., Graham, A., La Thangue, N.B., Mdm2 targets the p53 transcription cofactor JMY for degradation (2007) EMBO Rep, 8, pp. 84-90
  • Rinaldo, C., Prodosmo, A., Mancini, F., Iacovelli, S., Sacchi, A., Moretti, F., MDM2-regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis (2007) Mol Cell, 25, pp. 739-750
  • Shmueli, A., Oren, M., Mdm2: P53’s Lifesaver? (2007) Mol Cell, 25, pp. 794-796
  • Sudo, T., Ota, Y., Kotani, S., Nakao, M., Takami, Y., Takeda, S., Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells (2001) Embo J, 20, pp. 6499-6508
  • Obeyesekere, M.N., Tecarro, E., Lozano, G., Model predictions of MDM2 mediated cell regulation (2004) Cell Cycle, 3, pp. 655-661
  • Garcia, P., Cales, C., Endoreplication in megakaryoblastic cell lines is accompanied by sustained expression of G1/S cyclins and downregulation of cdc25C (1996) Oncogene, 13, pp. 695-703
  • Varmeh-Ziaie, S., Manfredi, J.J., The dual-specificity phosphatase Cdc25B, but not the closely related Cdc25C, is capable of inhibiting cellular proliferation in a manner dependent upon its catalytic activity (2007) J Biol Chem, 282, pp. 24633-24641

Citas:

---------- APA ----------
Giono, L.E., Resnick-Silverman, L., Carvajal, L.A., St Clair, S. & Manfredi, J.J. (2017) . Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase. Oncogene, 36(49), 6762-6773.
http://dx.doi.org/10.1038/onc.2017.254
---------- CHICAGO ----------
Giono, L.E., Resnick-Silverman, L., Carvajal, L.A., St Clair, S., Manfredi, J.J. "Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase" . Oncogene 36, no. 49 (2017) : 6762-6773.
http://dx.doi.org/10.1038/onc.2017.254
---------- MLA ----------
Giono, L.E., Resnick-Silverman, L., Carvajal, L.A., St Clair, S., Manfredi, J.J. "Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase" . Oncogene, vol. 36, no. 49, 2017, pp. 6762-6773.
http://dx.doi.org/10.1038/onc.2017.254
---------- VANCOUVER ----------
Giono, L.E., Resnick-Silverman, L., Carvajal, L.A., St Clair, S., Manfredi, J.J. Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase. Oncogene. 2017;36(49):6762-6773.
http://dx.doi.org/10.1038/onc.2017.254