DOCSLIB.ORG

Multiple Protein Phosphatases Are Required for Mitosis in Drosophila

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Multiple Protein Phosphatases Are Required for Mitosis in Drosophila Supplemental References S10. Margolis, S.S., Walsh, S., Weiser, D.C., Yoshida, M., Shenolikar, S., and Kornbluth, S. (2003). PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation. Embo J 22, 5734-5745. S11. Margolis, S.S., Perry, J.A., Weitzel, D.H., Freel, C.D., Yoshida, M., Haystead, T.A., and Kornbluth, S. (2006). A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25. Mol Biol Cell 17, 1779-1789. S12. Axton, J.M., Dombradi, V., Cohen, P.T., and Glover, D.M. (1990). One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis. Cell 63, 33-46. S13. Rogers, E., Bishop, J.D., Waddle, J.A., Schumacher, J.M., and Lin, R. (2002). The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis. J Cell Biol 157, 219-229. S14. Sassoon, I., Severin, F.F., Andrews, P.D., Taba, M.R., Kaplan, K.B., Ashford, A.J., Stark, M.J., Sorger, P.K., and Hyman, A.A. (1999). Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p. Genes Dev 13, 545-555. S15. Katayama, H., Zhou, H., Li, Q., Tatsuka, M., and Sen, S. (2001). Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J Biol Chem 276, 46219-46224. S16. Ohashi, S., Sakashita, G., Ban, R., Nagasawa, M., Matsuzaki, H., Murata, Y., Taniguchi, H., Shima, H., Furukawa, K., and Urano, T. (2006). Phospho-regulation of human protein kinase Aurora-A: analysis using anti-phospho-Thr288 monoclonal antibodies. Oncogene 25, 7691-7702. S17. Helps, N.R., Luo, X., Barker, H.M., and Cohen, P.T. (2000). NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem J 349, 509-518. S18. Glover, D.M., Leibowitz, M.H., McLean, D.A., and Parry, H. (1995). Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81, 95-105. S19. Meraldi, P., and Nigg, E.A. (2001). Centrosome cohesion is regulated by a balance of kinase and phosphatase activities. J Cell Sci 114, 3749-3757. S20. Eto, M., Elliott, E., Prickett, T.D., and Brautigan, D.L. (2002). Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation. J Biol Chem 277, 44013-44020. S21. Hsu, J.Y., Sun, Z.W., Li, X., Reuben, M., Tatchell, K., Bishop, D.K., Grushcow, J.M., Brame, C.J., Caldwell, J.A., Hunt, D.F., Lin, R., Smith, M.M., and Allis, C.D. (2000). Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102, 279-291. S22. Sugiyama, K., Sugiura, K., Hara, T., Sugimoto, K., Shima, H., Honda, K., Furukawa, K., Yamashita, S., and Urano, T. (2002). Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 21, 3103- 3111. S23. Goto, H., Yasui, Y., Nigg, E.A., and Inagaki, M. (2002). Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells 7, 11-17. S24. Dombradi, V., Axton, J.M., Barker, H.M., and Cohen, P.T. (1990). Protein phosphatase 1 activity in Drosophila mutants with abnormalities in mitosis and chromosome condensation. FEBS Lett 275, 39-43. S25. Dombradi, V., and Cohen, P.T. (1992). Protein phosphorylation is involved in the regulation of chromatin condensation during interphase. FEBS Lett 312, 21-26. S26. Baksa, K., Morawietz, H., Dombradi, V., Axton, M., Taubert, H., Szabo, G., Torok, I., Udvardy, A., Gyurkovics, H., Szoor, B., and et al. (1993). Mutations in the protein phosphatase 1 gene at 87B can differentially affect suppression of position-effect variegation and mitosis in Drosophila melanogaster. Genetics 135, 117-125. S27. Bloecher, A., and Tatchell, K. (2000). Dynamic localization of protein phosphatase type 1 in the mitotic cell cycle of Saccharomyces cerevisiae. J Cell Biol 149, 125-140. S28. Zeitlin, S.G., Shelby, R.D., and Sullivan, K.F. (2001). CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol 155, 1147-1157. S29. Andrews, P.D., and Stark, M.J. (2000). Type 1 protein phosphatase is required for maintenance of cell wall integrity, morphogenesis and cell cycle progression in Saccharomyces cerevisiae. J Cell Sci 113 ( Pt 3), 507-520. S30. Cheng, A., Dean, N.M., and Honkanen, R.E. (2000). Serine/threonine protein phosphatase type 1gamma1 is required for the completion of cytokinesis in human A549 lung carcinoma cells. J Biol Chem 275, 1846-1854. S31. Vereshchagina, N., Bennett, D., Szoor, B., Kirchner, J., Gross, S., Vissi, E., White-Cooper, H., and Alphey, L. (2004). The essential role of PP1beta in Drosophila is to regulate nonmuscle myosin. Mol Biol Cell 15, 4395-4405. S32. Kinoshita, N., Yamano, H., Niwa, H., Yoshida, T., and Yanagida, M. (1993). Negative regulation of mitosis by the fission yeast protein phosphatase ppa2. Genes Dev 7, 1059-1071. S33. Janssens, V., and Goris, J. (2001). Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353, 417-439. S34. Lin, F.C., and Arndt, K.T. (1995). The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosis. Embo J 14, 2745-2759. S35. Evans, D.R., and Stark, M.J. (1997). Mutations in the Saccharomyces cerevisiae type 2A protein phosphatase catalytic subunit reveal roles in cell wall integrity, actin cytoskeleton organization and mitosis. Genetics 145, 227- 241. S36. Snaith, H.A., Armstrong, C.G., Guo, Y., Kaiser, K., and Cohen, P.T. (1996). Deficiency of protein phosphatase 2A uncouples the nuclear and centrosome cycles and prevents attachment of microtubules to the kinetochore in Drosophila microtubule star (mts) embryos. J Cell Sci 109 ( Pt 13), 3001-3012. S37. Sonnichsen, B., Koski, L.B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A.M., Artelt, J., Bettencourt, P., Cassin, E., Hewitson, M., Holz, C., Khan, M., Lazik, S., Martin, C., Nitzsche, B., Ruer, M., Stamford, J., Winzi, M., Heinkel, R., Roder, M., Finell, J., Hantsch, H., Jones, S.J., Jones, M., Piano, F., Gunsalus, K.C., Oegema, K., Gonczy, P., Coulson, A., Hyman, A.A., and Echeverri, C.J. (2005). Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434, 462-469. S38. Van Hoof, C., and Goris, J. (2003). Phosphatases in apoptosis: to be or not to be, PP2A is in the heart of the question. Biochim Biophys Acta 1640, 97-104. S39. Kitajima, T.S., Sakuno, T., Ishiguro, K.I., Iemura, S.I., Natsume, T., Kawashima, S.A., and Watanabe, Y. (2006). Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441, 46-52. S40. Tang, Z., Shu, H., Qi, W., Mahmood, N., Mumby, M.C., and Yu, H. (2006). PP2A Is Required for Centromeric Localization of Sgo1 and Proper Chromosome Segregation. Dev Cell 10, 575-585. S41. Riedel, C.G., Katis, V.L., Katou, Y., Mori, S., Itoh, T., Helmhart, W., Galova, M., Petronczki, M., Gregan, J., Cetin, B., Mudrak, I., Ogris, E., Mechtler, K., Pelletier, L., Buchholz, F., Shirahige, K., and Nasmyth, K. (2006). Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441, 53-61. S42. Le Goff, X., Buvelot, S., Salimova, E., Guerry, F., Schmidt, S., Cueille, N., Cano, E., and Simanis, V. (2001). The protein phosphatase 2A B'-regulatory subunit par1p is implicated in regulation of the S. pombe septation initiation network. FEBS Lett 508, 136-142. S43. Jiang, W., and Hallberg, R.L. (2001). Correct regulation of the septation initiation network in Schizosaccharomyces pombe requires the activities of par1 and par2. Genetics 158, 1413-1429. S44. Deak, P., Donaldson, M., and Glover, D.M. (2003). Mutations in makos, a Drosophila gene encoding the Cdc27 subunit of the anaphase promoting complex, enhance centrosomal defects in polo and are suppressed by mutations in twins/aar, which encodes a regulatory subunit of PP2A. J Cell Sci 116, 4147-4158. S45. Minshull, J., Straight, A., Rudner, A.D., Dernburg, A.F., Belmont, A., and Murray, A.W. (1996). Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast. Curr Biol 6, 1609-1620. S46. Wang, Y., and Burke, D.J. (1997). Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple functions in mitosis and is required for the kinetochore/spindle checkpoint in Saccharomyces cerevisiae. Mol Cell Biol 17, 620-626. S47. Wang, Y., and Ng, T.Y. (2006). Phosphatase 2A negatively regulates mitotic exit in Saccharomyces cerevisiae. Mol Biol Cell 17, 80-89. S48. Yellman, C.M., and Burke, D.J. (2006). The role of Cdc55 in the spindle checkpoint is through regulation of mitotic exit in Saccharomyces cerevisiae. Mol Biol Cell 17, 658-666. S49. Mayer-Jaekel, R.E., Ohkura, H., Gomes, R., Sunkel, C.E., Baumgartner, S., Hemmings, B.A., and Glover, D.M. (1993). The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase. Cell 72, 621-633. S50. Kao, G., Tuck, S., Baillie, D., and Sundaram, M.V. (2004). C. elegans SUR-6/PR55 cooperates with LET-92/protein phosphatase 2A and promotes Raf activity independently of inhibitory Akt phosphorylation sites. Development 131, 755-765. S51. Fraser, A.G., Kamath, R.S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., and Ahringer, J. (2000). Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325-330. S52. Kinoshita, K., Nemoto, T., Nabeshima, K., Kondoh, H., Niwa, H., and Yanagida, M.
Load more

Recommended publications
  • 9. Atypical Dusps: 19 Phosphatases in Search of a Role
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital.CSIC Transworld Research Network 37/661 (2), Fort P.O. Trivandrum-695 023 Kerala, India Emerging Signaling Pathways in Tumor Biology, 2010: 185-208 ISBN: 978-81-7895-477-6 Editor: Pedro A. Lazo 9. Atypical DUSPs: 19 phosphatases in search of a role Yolanda Bayón and Andrés Alonso Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid c/ Sanz y Forés s/n, 47003 Valladolid, Spain Abstract. Atypical Dual Specificity Phosphatases (A-DUSPs) are a group of 19 phosphatases poorly characterized. They are included among the Class I Cys-based PTPs and contain the active site motif HCXXGXXR conserved in the Class I PTPs. These enzymes present a phosphatase domain similar to MKPs, but lack any substrate targeting domain similar to the CH2 present in this group. Although most of these phosphatases have no more than 250 amino acids, their size ranges from the 150 residues of the smallest A-DUSP, VHZ/DUSP23, to the 1158 residues of the putative PTP DUSP27. The substrates of this family include MAPK, but, in general terms, it does not look that MAPK are the general substrates for the whole group. In fact, other substrates have been described for some of these phosphatases, like the 5’CAP structure of mRNA, glycogen, or STATs and still the substrates of many A-DUSPs have not been identified. In addition to the PTP domain, most of these enzymes present no additional recognizable domains in their sequence, with the exception of CBM-20 in laforin, GTase in HCE1 and a Zn binding domain in DUSP12.
    [Show full text]
  • The Regulatory Roles of Phosphatases in Cancer
    Oncogene (2014) 33, 939–953 & 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14 www.nature.com/onc REVIEW The regulatory roles of phosphatases in cancer J Stebbing1, LC Lit1, H Zhang, RS Darrington, O Melaiu, B Rudraraju and G Giamas The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of various diseases, including different types of cancer, though phosphatases are relatively under-studied. Loss of phosphatases such as PTEN (phosphatase and tensin homologue deleted on chromosome 10), a known tumour suppressor, across tumour types lends credence to the development of phosphatidylinositol 3--kinase inhibitors alongside the use of phosphatase expression as a biomarker, though phase 3 trial data are lacking. In this review, we give an updated report on phosphatase dysregulation linked to organ-specific malignancies. Oncogene (2014) 33, 939–953; doi:10.1038/onc.2013.80; published online 18 March 2013 Keywords: cancer; phosphatases; solid tumours GASTROINTESTINAL MALIGNANCIES abs in sera were significantly associated with poor survival in Oesophageal cancer advanced ESCC, suggesting that they may have a clinical utility in Loss of PTEN (phosphatase and tensin homologue deleted on ESCC screening and diagnosis.5 chromosome 10) expression in oesophageal cancer is frequent, Cao et al.6 investigated the role of protein tyrosine phosphatase, among other gene alterations characterizing this disease. Zhou non-receptor type 12 (PTPN12) in ESCC and showed that PTPN12 et al.1 found that overexpression of PTEN suppresses growth and protein expression is higher in normal para-cancerous tissues than induces apoptosis in oesophageal cancer cell lines, through in 20 ESCC tissues.
    [Show full text]
  • Purification and Characterization of Two Members of the Protein
    PURIFICATION AND CHARACTERIZATION OF TWO MEMBERS OF THE PROTEIN TYROSINE PHOSPHATASE FAMILY: DUAL SPECIFICITY PHOSPHATASE PVP AND LOW MOLECULAR WEIGHT PHOSPHATASE WZB By Paula A. Livingston A Thesis Submitted to the Faculty of The Charles E. Schmidt College of Science in Partial Fulfillment for the Degree of Master of Science Florida Atlantic University Boca Raton, Florida December 2009 i ACKNOWLEDGMENTS The author wishes to thank her thesis advisor, Dr. Stefan Vetter, and the members of her committee, Dr. Estelle Leclerc and Dr. Predrag Cudic, for their advice and support throughout her years at Florida Atlantic University. The author also wishes to thank her family for their unending support and encouragement without which this would not have been possible. The author would also like to thank her nephew and niece, Griffin and Skye, for inspiring her throughout her entire graduate experience. iii ABSTRACT Author: Paula A. Livingston Title: Purification and Characterization of Two Members of the Protein Tyrosine Phosphatase Family: Dual Specificity Phosphatase PVP and Low Molecular Weight Phosphatase WZB Institution: Florida Atlantic University Thesis Advisor: Dr. Stefan W. Vetter Degree: Master of Science Year: 2009 Two protein tyrosine phosphatases, dual specificity phosphatase PVP and low molecular weight phosphatase WZB were purified and characterized. PVP was expressed as inclusion bodies and a suitable purification and refolding method was devised. Enzyme kinetics revealed that p-nitrophenylphosphate and β-naphthyl phosphate were substrates with KM of 4.0mM and 8.1mM respectively. PVP showed no reactivity towards phosphoserine. Kinetic characterization of WZB showed that only p- nitrophenylphosphate was a substrate with no affinity for β-naphthyl phosphate and phosphoserine.
    [Show full text]
  • Dephosphorylation of Threonine-14 and Tyrosine-15
    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 3521-3524, April 1993 Biochemistry Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15 BYRON SEBASTIAN*t, AKIRA KAKIZUKAt, AND TONY HUNTER* *Molecular Biology and Virology Laboratory and tGene Expression Laboratory, The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, CA 92186; and tDepartment of Biology, University of California at San Diego, La Jolla, CA 92093 Communicated by Renato Dulbecco, January 4, 1993 (receivedfor review December 15, 1992) ABSTRACT Recent evidence has suggested that human in regulating entry into S phase is suggested by reports that cyclin-dependent kinase 2 (CDK2) is an essential regulator of cycin E-associated kinase activity peaks in G1 (23, 24) and cell cycle progression through S phase. CDK2 is known to that overexpression ofcyclin E decreases the length ofG1 and complex with at least two distinct human cyclins, E and A. The diminishes the dependency of proliferating human cells on kinase activity of these complexes peaks in G1 and S phase, growth factors (23). Although both CDK2 and CDC2 asso- respectively. The vertebrate CDC2/cyclin Bi complex is an ciate with cyclin E, the predominant complex appears to be essential regulator of the onset of mitosis and is inhibited by CDK2/cyclin E. A role for CDK2/cyclin A in regulating phosphorylation of CDC2 on Thr-14 and Tyr-15. In vitro, progression through S phase is suggested by observations CDC2/cyclin Bi is activated by treatment with the members of that microinjection of either anti-cyclin A antibodies or the Cdc25 family of phosphatases.
    [Show full text]
  • Dual-Specificity Phosphatases in Immunity and Infection
    International Journal of Molecular Sciences Review Dual-Specificity Phosphatases in Immunity and Infection: An Update Roland Lang * and Faizal A.M. Raffi Institute of Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany * Correspondence: [email protected]; Tel.: +49-9131-85-22979 Received: 15 May 2019; Accepted: 30 May 2019; Published: 2 June 2019 Abstract: Kinase activation and phosphorylation cascades are key to initiate immune cell activation in response to recognition of antigen and sensing of microbial danger. However, for balanced and controlled immune responses, the intensity and duration of phospho-signaling has to be regulated. The dual-specificity phosphatase (DUSP) gene family has many members that are differentially expressed in resting and activated immune cells. Here, we review the progress made in the field of DUSP gene function in regulation of the immune system during the last decade. Studies in knockout mice have confirmed the essential functions of several DUSP-MAPK phosphatases (DUSP-MKP) in controlling inflammatory and anti-microbial immune responses and support the concept that individual DUSP-MKP shape and determine the outcome of innate immune responses due to context-dependent expression and selective inhibition of different mitogen-activated protein kinases (MAPK). In addition to the canonical DUSP-MKP, several small-size atypical DUSP proteins regulate immune cells and are therefore also reviewed here. Unexpected and complex findings in DUSP knockout mice pose new questions regarding cell type-specific and redundant functions. Another emerging question concerns the interaction of DUSP-MKP with non-MAPK binding partners and substrate proteins.
    [Show full text]
  • A Novel Synthetic Inhibitor of CDC25 Phosphatases: BN82002
    [CANCER RESEARCH 64, 3320–3325, May 1, 2004] A Novel Synthetic Inhibitor of CDC25 Phosphatases: BN82002 Marie-Christine Brezak,1 Muriel Quaranta,2 Odile Monde´sert,2 Marie-Odile Galcera,1 Olivier Lavergne,1 Fre´de´ric Alby,2 Martine Cazales,2 Ve´ronique Baldin,2 Christophe Thurieau,1 Jeremiath Harnett,1 Christophe Lanco,1 Philip G. Kasprzyk,1,3 Gregoire P. Prevost,1 and Bernard Ducommun2 1IPSEN, Institut Henri Beaufour, Les Ulis Cedex, France; 2Laboratoire de Biologie Cellulaire et Moleculaire du Controle de la Proliferation-Centre National de la Recherche Scientifique UMR5088-IFR109 “Institut d’Exploration Fonctionnelle des Ge´nomes,” Universite´ Paul Sabatier, Toulouse, France; and 3IPSEN, Biomeasure, Milford, Massachusetts ABSTRACT B at mitosis (2) where it dephosphorylates tyrosine 15 and threonine 14. It also plays a role in the control of the initiation of S phase (5). CDC25 dual-specificity phosphatases are essential regulators that de- The elucidation of the specific role of each isoform at specific stages phosphorylate and activate cyclin-dependent kinase/cyclin complexes at of the cell cycle is a major issue that is still currently under investi- key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative gation. agents. Here we report the identification of a new CDC25 inhibitor and Overexpression of CDC25A and B, but not C, has been observed in the characterization of its effects at the molecular and cellular levels, and a variety of cancers (i.e., breast, ovary, head and neck, and colon) with in animal models. a striking association with tumor aggressiveness and poor prognosis BN82002 inhibits the phosphatase activity of recombinant human (6–9).
    [Show full text]
  • Characterization of a Murine Gene Encoding a Developmentally Regulated Cytoplasmic Dual-Specificity Mitogen-Activated Protein Kinase Phosphatase Robin J
    Biochem. J. (2002) 364, 145–155 (Printed in Great Britain) 145 Characterization of a murine gene encoding a developmentally regulated cytoplasmic dual-specificity mitogen-activated protein kinase phosphatase Robin J. DICKINSON*, David J. WILLIAMS*, David N. SLACK*, Jill WILLIAMSON†, Ole-Morten SETERNES* and Stephen M. KEYSE*1 *Cancer Research UK, Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital, Dundee DD1 9SY, Scotland, U.K., and †Cancer Research UK, Cytogenetics Laboratory, Lincoln’s Inn Fields, London WC2A 3PX, U.K. Mitogen-activated protein kinases (MAPKs) play a vital role in mammalian cells, the Pyst3 protein is predominantly cytoplasmic. cellular growth control, but far less is known about these Furthermore, leptomycin B causes a complete redistribution of signalling pathways in the context of embryonic development. the protein to the nucleus, implicating a CRM (chromosomal Duration and magnitude of MAPK activation are crucial factors region maintenance)1\exportin 1-dependent nuclear export sig- in cell fate decisions, and reflect a balance between the activities nal in determining the subcellular localization of this enzyme. of upstream activators and specific MAPK phosphatases Finally, whole-mount in situ hybridization studies in mouse (MKPs). Here, we report the isolation and characterization of embryos reveal that the Pyst3 gene is expressed specifically in the the murine Pyst3 gene, which encodes a cytosolic dual-specificity placenta, developing liver and in migratory muscle cells. Our MKP. This enzyme selectively interacts with, and is catalytically results suggest that this enzyme may have a critical role in activated by, the ‘classical’ extracellular signal-regulated kinases regulating the activity of MAPK signalling during early de- (ERKs) 1 and 2 and, to a lesser extent, the stress-activated velopment and organogenesis.
    [Show full text]
  • CDC25 Phosphatases in Cancer Cells…
    REVIEWS CDC25 phosphatases in cancer cells: key players? Good targets? Rose Boutros*, Valérie Lobjois* and Bernard Ducommun*‡ Abstract | Cell division cycle 25 (CDC25) phosphatases regulate key transitions between cell cycle phases during normal cell division, and in the event of DNA damage they are key targets of the checkpoint machinery that ensures genetic stability. Taking only this into consideration, it is not surprising that CDC25 overexpression has been reported in a significant number of human cancers. However, in light of the significant body of evidence detailing the stringent complexity with which CDC25 activities are regulated, the significance of CDC25 overexpression in a subset of cancers and its association with poor prognosis are proving difficult to assess. We will focus on the roles of CDC25 phosphatases in both normal and abnormal cell proliferation, provide a critical assessment of the current data on CDC25 overexpression in cancer, and discuss both current and future therapeutic strategies for targeting CDC25 activity in cancer treatment. Dual-specificity protein The cell division cycle 25 (CDC25) family of proteins are Among the different species, the catalytic domains of phosphatase highly conserved dual specificity phosphatases that acti- CDC25 proteins are quite conserved compared with A phosphoprotein vate cyclin-dependent kinase (CDK) complexes, which in the regulatory regions, which are far more diverse and phosphatase that is able to turn regulate progression through the cell division cycle. further subjected to alternative splicing events that gen- hydrolyse the phosphate ester 8 bond on both a tyrosine and a CDC25 phosphatases are also key components of the erate at least two variants for CDC25A and five each for 9,10 8,11 threonine or serine residue on checkpoint pathways that become activated in the event of CDC25B and CDC25C (FIG.
    [Show full text]
  • PTEN Mutation: Many Birds with One Stone in Tumorigenesis WEIJIN LIU 1, YONGGANG ZHOU 2, SVEN N
    ANTICANCER RESEARCH 28 : 3613-3620 (2008) Review PTEN Mutation: Many Birds with One Stone in Tumorigenesis WEIJIN LIU 1, YONGGANG ZHOU 2, SVEN N. RESKE 3 and CHANGXIAN SHEN 4 1Department of Life Sciences, Huaihua University, Huaihua, P. R. of China; 2German Cancer Research Center, Heidelberg; 3Department of Nuclear Medicine, University of Ulm, Ulm, Germany; 4Department of Molecular Pharmacology, St. Jude Children’s Research Hospital, Memphis, TN, U.S.A. Abstract. The PTEN (phosphatase and tensin homolog combination with the loss of certain other tumor suppressor deleted on chromosome ten) tumor suppressor gene is genes or with genetically engineered reduction of PTEN mutated in a wide range of malignancies and recent studies expression just below heterozygosity (3-7). have demonstrated that PTEN prevents tumorigenesis PTEN is a multiple-domain polypeptide of 403 amino acids. through multiple mechanisms. PTEN functions as a plasma- It contains an amino-terminal phosphatase domain homologous membrane lipid phosphatase that antagonizes the PI3K to chicken tensin and a C2 domain, which mediates the (phosphoinositide 3 kinase)-AKT pathway. PTEN physically association of signal proteins to plasma membranes. The C- and genetically interacts with the central genome guardian terminal PDZ (PSD95, DlgA and Zo-1) domain-binding p53. PTEN also associates with the centromeric protein sequence and PEST (rich in proline, glutamate, serine, and CENP-C to maintain centromere integrity and suppresses threonine residues) domain regulate protein stability via the chromosomal instability from DNA double-strand breaks ubiquitin-proteasome pathway (2). PTEN has two canonical (DSBs) through transcriptional regulation of Rad51 PEST domains, which is a signature in many short-lived (radiosensitive yeast mutant 51).
    [Show full text]
  • Expression Profile of Tyrosine Phosphatases in HER2 Breast
    Cellular Oncology 32 (2010) 361–372 361 DOI 10.3233/CLO-2010-0520 IOS Press Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors Maria Antonietta Lucci a, Rosaria Orlandi b, Tiziana Triulzi b, Elda Tagliabue b, Andrea Balsari c and Emma Villa-Moruzzi a,∗ a Department of Experimental Pathology, University of Pisa, Pisa, Italy b Molecular Biology Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy c Department of Human Morphology and Biomedical Sciences, University of Milan, Milan, Italy Abstract. Background: HER2-overexpression promotes malignancy by modulating signalling molecules, which include PTPs/DSPs (protein tyrosine and dual-specificity phosphatases). Our aim was to identify PTPs/DSPs displaying HER2-associated expression alterations. Methods: HER2 activity was modulated in MDA-MB-453 cells and PTPs/DSPs expression was analysed with a DNA oligoar- ray, by RT-PCR and immunoblotting. Two public breast tumor datasets were analysed to identify PTPs/DSPs differentially ex- pressed in HER2-positive tumors. Results: In cells (1) HER2-inhibition up-regulated 4 PTPs (PTPRA, PTPRK, PTPN11, PTPN18) and 11 DSPs (7 MKPs [MAP Kinase Phosphatases], 2 PTP4, 2 MTMRs [Myotubularin related phosphatases]) and down-regulated 7 DSPs (2 MKPs, 2 MTMRs, CDKN3, PTEN, CDC25C); (2) HER2-activation with EGF affected 10 DSPs (5 MKPs, 2 MTMRs, PTP4A1, CDKN3, CDC25B) and PTPN13; 8 DSPs were found in both groups. Furthermore, 7 PTPs/DSPs displayed also altered protein level. Analysis of 2 breast cancer datasets identified 6 differentially expressed DSPs: DUSP6, strongly up-regulated in both datasets; DUSP10 and CDC25B, up-regulated; PTP4A2, CDC14A and MTMR11 down-regulated in one dataset.
    [Show full text]
  • Dual Specificity Phosphatases from Molecular Mechanisms to Biological Function
    International Journal of Molecular Sciences Dual Specificity Phosphatases From Molecular Mechanisms to Biological Function Edited by Rafael Pulido and Roland Lang Printed Edition of the Special Issue Published in International Journal of Molecular Sciences www.mdpi.com/journal/ijms Dual Specificity Phosphatases Dual Specificity Phosphatases From Molecular Mechanisms to Biological Function Special Issue Editors Rafael Pulido Roland Lang MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editors Rafael Pulido Roland Lang Biocruces Health Research Institute University Hospital Erlangen Spain Germany Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal International Journal of Molecular Sciences (ISSN 1422-0067) from 2018 to 2019 (available at: https: //www.mdpi.com/journal/ijms/special issues/DUSPs). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03921-688-8 (Pbk) ISBN 978-3-03921-689-5 (PDF) c 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editors ....................................
    [Show full text]
  • Regulation of the Cdc25a Gene by the Human Papillomavirus Type 16 E7 Oncogene
    Oncogene (2001) 20, 543 ± 550 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc ORIGINAL PAPERS Regulation of the Cdc25A gene by the human papillomavirus Type 16 E7 oncogene Stephanie C Katich1, Karin Zerfass-Thome1 and Ingrid Homann*,1 1Angewandte Tumorvirologie (F0400), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany Cdc25A is a tyrosine phosphatase that is involved in the (Homann et al., 1993). Recent work indicates that regulation of the G1/S phase transition by activating Cdc25B seems to play the role of a `starter phosphatase' cyclin E/Cdk2 and cyclin A/Cdk2 complexes through by activating cyclin B/Cdk1 in order to initiate the removal of inhibitory phosphorylations. The E6 and E7 positive feedback mechanism (Lammer et al., 1998; oncoproteins of the high-risk human papillomaviruses Karlsson et al., 1999). Cdc25 phosphatases are main (HPV) interact with and functionally abrogate the p53 players of the G2 arrest caused by DNA damage or in the and pRB proteins, respectively. In the present study we presence of unreplicated DNA (Sanchez et al., 1997; have investigated the regulation of the Cdc25A promoter Peng et al., 1997). Cdc25A and B are putative human during G1 and S-phases of the cell cycle and by the oncogenes (Galaktionov et al., 1995, 1997). The Cdc25A HPV-16 E7 oncoprotein. Serum induction leads to a phosphatase plays a crucial role at the G1/S phase derepression of the Cdc25A promoter and can be transition as shown by microinjection experiments using mediated through two E2F binding sites, E2F-A and Cdc25A speci®c antibodies (Homann et al., 1994) and E2F-C.
    [Show full text]