Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma

0455787 - ÚMG 2016 RIV US eng J - Článek v odborném periodiku
Dráberová, Eduarda - D'Agostino, L. - Caracciolo, V. - Sládková, Vladimíra - Sulimenko, Tetyana - Sulimenko, Vadym - Sobol, Margaryta - Maounis, N.F. - Tzelepis, E. - Mahera, E. - Křen, L. - Legido, A. - Giordano, A. - Moerk, S. - Hozák, Pavel - Dráber, Pavel - Katsetos, C.D.
Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma.
Journal of Neuropathology and Experimental Neurology. Roč. 74, č. 7 (2015), s. 723-742. ISSN 0022-3069. E-ISSN 1554-6578
Grant CEP: GA MŠMT LH12050; GA MZd NT14467; GA ČR GAP302/12/1673; GA TA ČR(CZ) TE01020118; GA MPO FR-TI3/588
Grant ostatní: GA AV ČR M200521203PIPP; St. Christopher's Hospital for Children Reunified Endowment(US) 323256
Institucionální podpora: RVO:68378050
Klíčová slova: Gamma-tubulin * Gamma-tubulin complex proteins * GCP2 * Glioma * Glioblastoma * Nucleolus
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 3.432, rok: 2015

The expression, cellular distribution, and subcellular sorting of the microtubule (MT)-nucleating -tubulin small complex (TuSC) 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 TuSC 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 -tubulin in the nucleoli as confirmed by reciprocal immunoprecipitation experiments and immunoelectron microscopy. GCP2 and GCP3 depletion caused accumulation of cells in G(2)/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 G(2)/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 TuSC protein dysregulation in glioblastomas may be linked to altered transcriptional checkpoint activity or interaction with signaling pathways associated with a malignant phenotype.
Trvalý link: http://hdl.handle.net/11104/0256409