Logo image
Back
Overexpression and Nucleolar Localization of gamma-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma
Journal article   Open access   Peer reviewed

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

Eduarda Draberova, Luca D'Agostino, Valentina Caracciolo, Vladimira Sladkova, Tetyana Sulimenko, Vadym Sulimenko, Margaryta Sobol, Nicoletta F. Maounis, Elias Tzelepis, Eleni Mahera, …
Journal of neuropathology and experimental neurology, v 74(7), pp 723-742
01 Jul 2015
DOI: https://doi.org/10.1097/NEN.0000000000000212
PMID: 26079448
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://academic.oup.com/jnen/article-pdf/74/7/723/17420276/74-7-723.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1097/NEN.0000000000000212View
Published, Version of Record (VoR) Open

Abstract

Clinical Neurology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Pathology Science & Technology
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.

Metrics

8 Record Views
28 citations in Web of Science
28 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Clinical Neurology
Neurosciences
Pathology
Logo image