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Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma.
Dráberová, Eduarda; D'Agostino, Luca; Caracciolo, Valentina; Sládková, Vladimíra; Sulimenko, Tetyana; Sulimenko, Vadym; Sobol, Margaryta; Maounis, Nicoletta F; Tzelepis, Elias; Mahera, Eleni; Kren, Leos; Legido, Agustin; Giordano, Antonio; Mörk, Sverre; Hozák, Pavel; Dráber, Pavel; Katsetos, Christos D.
Afiliación
  • Dráberová E; From the Departments of Biology of Cytoskeleton (ED, VS, TS, VS, PD) and Biology of the Nucleus (MS, PH), Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Department of Pediatrics (LD, ET, AL, CDK), Drexel University College of Medicine, Section of Pediatric Neurology and Neurooncology Program (AL, CDK), St. Christopher's Hospital for Children, and Department of Pathology and Laboratory Medicine (NFM, CDK) Drexel University College of Medicine,
J Neuropathol Exp Neurol ; 74(7): 723-42, 2015 Jul.
Article en En | MEDLINE | ID: mdl-26079448
The expression, cellular distribution, and subcellular sorting of the microtubule (MT)-nucleating γ-tubulin small complex (γTuSC) proteins, GCP2 and GCP3, were studied in human glioblastoma cell lines and in clinical tissue samples representing all histologic grades of adult diffuse astrocytic gliomas (n = 54). Quantitative real-time polymerase chain reaction revealed a significant increase in the expression of GCP2 and GCP3 transcripts in glioblastoma cells versus normal human astrocytes; these were associated with higher amounts of both γTuSC proteins. GCP2 and GCP3 were concentrated in the centrosomes in interphase glioblastoma cells, but punctate and diffuse localizations were also detected in the cytosol and nuclei/nucleoli. Nucleolar localization was fixation dependent. GCP2 and GCP3 formed complexes with γ-tubulin in the nucleoli as confirmed by reciprocal immunoprecipitation experiments and immunoelectron microscopy. GCP2 and GCP3 depletion caused accumulation of cells in G2/M and mitotic delay but did not affect nucleolar integrity. Overexpression of GCP2 antagonized the inhibitory effect of the CDK5 regulatory subunit-associated tumor suppressor protein 3 (C53) on DNA damage G2/M checkpoint activity. Tumor cell GCP2 and GCP3 immunoreactivity was significantly increased over that in normal brains in glioblastoma samples; it was also associated with microvascular proliferation. These findings suggest that γTuSC protein dysregulation in glioblastomas may be linked to altered transcriptional checkpoint activity or interaction with signaling pathways associated with a malignant phenotype.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Nucléolo Celular / Glioblastoma / Proteínas Asociadas a Microtúbulos Límite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Neuropathol Exp Neurol Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Nucléolo Celular / Glioblastoma / Proteínas Asociadas a Microtúbulos Límite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Neuropathol Exp Neurol Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido