Artículo

Santori, M.I.; Laría, S.; Gómez, E.B.; Espinosa, I.; Galanti, N.; Téllez-Iñón, M.T. "Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi" (2002) Molecular and Biochemical Parasitology. 121(2):225-232
La versión final de este artículo es de uso interno. El editor solo permite incluir en el repositorio el artículo en su versión post-print. Por favor, si usted la posee enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Trypanosoma cruzi CRK3 gene encodes a Cdc2p related protein kinase (CRK). To establish if it has a role in the regulation of the parasite cell cycle we studied CRK3 expression and activity throughout three life cycle stages. CRK3 from epimastigote soluble extracts interacted with p13suc1-beads. Endogenous CRK3 phosphorylated histone H1 and this activity was inhibited by specific CDK inhibitors: Olomoucine, Flavopiridol and Roscovitine. Flavopiridol partially inhibited the growth of T. cruzi epimastigotes at 50 nM, the lowest concentration used, but even with the highest (5 μM), cell growth was not completely arrested. CRK3 from Flavopiridol-inhibited epimastigote extracts exhibited a dose dependent inhibition of histone H1 phosphorylation. T. cruzi p13suc1-binding CRK displayed the same inhibition profile. This suggests that CRK3 is the enzyme responsible for the majority of the kinase activity associated with p13suc1. CRK3 activity of hydroxyurea (HU) synchronized epimastigotes peaked in G2/M boundary while the kinase activity associated to p13suc1-beads increased at the same time point but remained high until late G2/M. In addition, CRK3 expression was constant during the cell cycle. This is a common pattern of CDK activity regulation. Taken together, these results support the idea that CRK3 is involved in control of the cell cycle in T. cruzi. © 2002 Elsevier Science B.V. All rights reserved.

Registro:

Documento: Artículo
Título:Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi
Autor:Santori, M.I.; Laría, S.; Gómez, E.B.; Espinosa, I.; Galanti, N.; Téllez-Iñón, M.T.
Filiación:Instituto De Investigaciones En Ingeniería Genética Y Biología Molecular, Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires (UBA), Vuelta de Obligado 2490, (1428) Buenos Aires, Argentina
Programa De Desarrollo De Biología Molecular Y Celular, Instituto De Ciencias Biomédicas (ICBM), Universidad De Chile, Santiago, Chile
Palabras clave:Cell cycle control; Cyclin-dependent kinase; Flavopiridol; Hydroxyurea synchronization; Trypanosoma cruzi; flavopiridol; histone H1; hydroxyurea; olomoucine; protein; protein kinase; protein kinase inhibitor; protein p13; roscovitine; unclassified drug; article; cell cycle; cell cycle G2 phase; cell division; cell synchronization; concentration response; developmental stage; drug effect; enzyme activity; enzyme binding; epimastigote; gene expression; growth inhibition; mitosis inhibition; nonhuman; parasite development; phosphorylation; priority journal; protein interaction; regulatory mechanism; Trypanosoma cruzi; Animals; CDC2 Protein Kinase; Cell Cycle; Cyclin-Dependent Kinases; Enzyme Inhibitors; Flavonoids; Gene Expression Regulation; Hydroxyurea; Piperidines; Protozoan Proteins; Trypanosoma cruzi; Trypanosoma; Trypanosoma cruzi
Año:2002
Volumen:121
Número:2
Página de inicio:225
Página de fin:232
DOI: http://dx.doi.org/10.1016/S0166-6851(02)00039-7
Título revista:Molecular and Biochemical Parasitology
Título revista abreviado:Mol. Biochem. Parasitol.
ISSN:01666851
CODEN:MBIPD
CAS:CDC2 Protein Kinase, EC 2.7.1.37; CRK3 kinase, protozoa, EC 2.7.10.-; Cyclin-Dependent Kinases, EC 2.7.1.37; Enzyme Inhibitors; Flavonoids; flavopiridol, 146426-40-6; Hydroxyurea, 127-07-1; Piperidines; Protozoan Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01666851_v121_n2_p225_Santori

Referencias:

  • De Souza, W., Cell biology of Trypanosoma cruzi (1984) Int. Rev. Cytol., 86, pp. 197-283
  • Tyler, K.M., Engman, D.M., The life cycle of Trypanosoma cruzi revisited (2001) Int. J. Parasitol., 31, pp. 472-481
  • Turner, C.M.R., Cell cycle co-ordination in Trypanosomes (1992) Parasitol. Today, 8, pp. 3-4
  • Morgan, D.O., Principles of CDK regulation (1995) Nature, 374, pp. 131-134
  • Pines, J., Cyclins and cyclin-dependent kinases: A biochemical view (1995) Biochem. J., 308, pp. 697-711
  • Pines, J., Hunter, T., Cyclin-dependent kinases: An embarrassment of riches? (1995) Cell cycle control, pp. 144-176. , C. Hutchison, & D.N. Glover. Oxford: IRL Press
  • Meijer, L., Chemical inhibitors of cyclin-dependent kinases (1996) Trends Cell. Biol., 3, pp. 393-397
  • Meijer, L., Kim, S.H., Chemical inhibitors of cyclin-dependent kinases (1997) Methods Enzymol., 283, pp. 113-128
  • Czech, J., Hoffman, D., Naik, R., Sedlacek, H.H., Antitumoral activity of flavone L86 8275 (1995) Int. J. Oncol., 6, pp. 31-36
  • Carlson, B.A., Dubay, M.M., Sausville, E.A., Brizuela, L., Worland, P.J., Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase CDK2 and CDK4 in human breast carcinoma cells (1996) Cancer Res., 56, pp. 2973-2978
  • Worland, P.J., Kaur, G., Stetler-Stevenson, M., Sebers, S., Sartor, O., Sausville, E.A., Alteration of the phosphorylation state of p34Cdc2p kinase by the flavone L86-8275 in breast carcinoma cells. Correlation with decreased H1 kinase activity (1993) Biochem. Pharmacol., 46, pp. 1831-1840
  • Graeser, R., Wernli, B., Franklin, R.M., Kappes, B., Plasmodium falciparum protein kinase 5 and the malarial nuclear division cycles (1996) Mol. Biol. Parasitol., 82, pp. 37-49
  • Oikonomakos, N., Schnier, J., Zographos, S., Skamnaki, V., Tsitsanou, K., Johnson, L., Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site (2000) J. Biol. Chem., 275, pp. 34566-34573
  • Gómez, E., Kornblihtt, A.R., Téllez-Iñón, M.T., Cloning of a Cdc2p-related protein kinase from the parasite Trypanosoma cruzi that interacts with mammalian cyclins (1998) Mol. Biol. Parasitol., 91, pp. 337-351
  • Gómez, E.B., Santori, M.I., Laria, S., Engel, J.C., Swindle, J., Eisen, H., Szankasi, P., Téllez-Iñón, M.T., Characterization of the Trypanosoma cruzi Cdc2p-related protein kinase 1 and identification of three novel associating cyclins (2001) Mol. Biochem. Parasitol., 113, pp. 97-108
  • Mottram, J.C., Kinnaird, J.H., Shiels, B., Tait, A., Barry, D., A novel Cdc2p-related protein kinase from Leishmania mexicana LmmCRK1, is post-translationally regulated during the life cycle (1993) J. Biol. Chem., 268, pp. 21044-21052
  • Mottram, J.C., Smith, G., A family of trypanosome Cdc2p-related protein kinases (1995) Gene, 162, pp. 147-152
  • Mottram, J., McCready, P., Brown, K., Grant, K., Gene disruption indicate an essential function for the LmmCRK1 Cdc2p-related kinase of Leishmania mexicana (1996) Mol. Microbiol., 22, pp. 573-582
  • Grant, K.M., Hassan, P., Anderson, J.S., Mottram, J.C., The crk3 gene of Leishmania mexicana encodes a stage-regulated Cdc2p-related histone H1 kinase that associates with p12cks1 (1998) J. Biol. Chem., 24, pp. 10153-10159
  • Wang, Y., Dimitrov, K., Garrity, L., Sazer, S., Beverley, S., Stage-specific activity of the Leishmania major CRK3 kinase and functional rescue of a Schizosaccharomyces pombe Cdc2p mutant (1998) Mol. Biochem. Parasitol., 96, pp. 139-150
  • Hassan, P., Fergusson, D., Grant, K.M., Mottram, J.C., The CRK3 protein kinase is essential for cell cycle progression of Leishmania mexicana (2001) Mol. Biochem. Parasitol., 113, pp. 189-198
  • Mottram, J.C., Grant, K.M., Leishmania mexicana p12cks1, a functional homologue of fission yeast p13suc1, associates with a stage-regulated histone H1 kinase (1996) Biochem. J., 316, pp. 833-839
  • Gómez, M.L., Erijman, L., Araujo, S., Torres, H.N., Téllez-Inón, M.T., Protein kinase C in Trypanosoma cruzi epimastigote forms: Partial purification and characterization (1989) Mol. Biochem. Parasitol., 36, pp. 101-108
  • Andrews, N., Colli, W., Adhesion and interiorization of Trypanosoma cruzi in mammalian cells (1982) J. Protozool., 29, pp. 264-269
  • Galanti, N., Dvorak, J.A., Grenet, J., McDaniel, J.P., Hydroxyurea-induced synchrony of DNA replication in kinetoplastida (1994) Exp. Cell. Res., 214, pp. 225-230
  • Rojas, M.V., Galanti, N., Relationship between DNA methylation and cell proliferation in Trypanosoma cruzi (1991) FEBS Lett., 295, pp. 31-34
  • Brizuela, L., Draetta, G., Beach, D., P13Suc1p acts in the fission yeast cell division cycle as a component of the p34Cdc2p protein kinase (1987) EMBO J., 6, pp. 3507-3514
  • Tang, L., Pelech, L., Berger, J.D., A Cdc2p-like kinase associated with commitment to division in Paramecium tetraurelia (1994) J. Euk. Microbiol., 41, pp. 381-387
  • Takahashi, M., Amin, N., Grant, P., Pant, H.C., P13Suc1 associates with a Cdc2p-like kinase in a multimeric cytoskeletal complex in squid axoplasm (1995) J. Neurosci., 15, pp. 6222-6229
  • Recinos, R.F., Kirchhoff, L.V., Donelson, J.E., Cell cycle expression of histone genes in Trypanosoma cruzi (2001) Mol. Biochem. Parasitol., 113, pp. 215-222
  • Birck, C., Raynaud-Messina, B., Samama, J.P., Oligomerization state in solution of the cell cycle regulators p13suc1 from the fission yeast and p9cksphy from the myxomycete Physarum, two members of the cks family (1995) FEBS Lett., 363, pp. 145-150
  • Parge, H.E., Arvai, A.S., Murtari, D.J., Reed, S.I., Tainer, J.A., Human CksHs2 atomic structure: A role for its hexameric assembly in cell cycle control (1993) Science, 262, pp. 387-395
  • Arvai, A.S., Bourne, Y., Hickey, M.J., Tainer, J.A., Crystal structure of the human cell cycle protein CksHs1: Single domain fold with similarity to kinase N-lobe domain (1995) J. Mol. Biol., 249, pp. 835-842
  • Mutomba, M.C., Wang, C.C., Effect of aphidicolin and hydroxyurea on the cell cycle and differentiation of Trypanosoma brucei bloodstream form (1996) Mol. Biochem. Parasitol., 80, pp. 89-102
  • Brun, R., Hydroxyurea: Effect on growth, structure, and [3H]thymidine uptake of Trypanosoma brucei procyclic culture forms (1980) J. Protozool., 27, pp. 122-128

Citas:

---------- APA ----------
Santori, M.I., Laría, S., Gómez, E.B., Espinosa, I., Galanti, N. & Téllez-Iñón, M.T. (2002) . Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi. Molecular and Biochemical Parasitology, 121(2), 225-232.
http://dx.doi.org/10.1016/S0166-6851(02)00039-7
---------- CHICAGO ----------
Santori, M.I., Laría, S., Gómez, E.B., Espinosa, I., Galanti, N., Téllez-Iñón, M.T. "Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi" . Molecular and Biochemical Parasitology 121, no. 2 (2002) : 225-232.
http://dx.doi.org/10.1016/S0166-6851(02)00039-7
---------- MLA ----------
Santori, M.I., Laría, S., Gómez, E.B., Espinosa, I., Galanti, N., Téllez-Iñón, M.T. "Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi" . Molecular and Biochemical Parasitology, vol. 121, no. 2, 2002, pp. 225-232.
http://dx.doi.org/10.1016/S0166-6851(02)00039-7
---------- VANCOUVER ----------
Santori, M.I., Laría, S., Gómez, E.B., Espinosa, I., Galanti, N., Téllez-Iñón, M.T. Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi. Mol. Biochem. Parasitol. 2002;121(2):225-232.
http://dx.doi.org/10.1016/S0166-6851(02)00039-7