Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26079448
DOI
10.1097/nen.0000000000000212
PII: 00005072-201507000-00008
Knihovny.cz E-resources
- MeSH
- Cell Nucleolus metabolism MeSH
- Cell Cycle physiology MeSH
- Zebrafish MeSH
- Glioblastoma metabolism pathology ultrastructure MeSH
- Chickens MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Brain Neoplasms metabolism pathology ultrastructure MeSH
- DNA Damage genetics MeSH
- Microtubule-Associated Proteins genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic physiology MeSH
- Protein Transport MeSH
- Tubulin metabolism MeSH
- Anura MeSH
- Animals MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Tumor Suppressor Protein p53 MeSH
- Microtubule-Associated Proteins MeSH
- TUBGCP2 protein, human MeSH Browser
- TUBGCP3 protein, human MeSH Browser
- Tubulin MeSH
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.
References provided by Crossref.org
Anti-Cancer Potential of a new Derivative of Caffeic Acid Phenethyl Ester targeting the Centrosome
γ-Tubulin in microtubule nucleation and beyond
C53 Interacting with UFM1-Protein Ligase 1 Regulates Microtubule Nucleation in Response to ER Stress
Dysregulation of Microtubule Nucleating Proteins in Cancer Cells
The actin regulator profilin 1 is functionally associated with the mammalian centrosome
Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed?
Regulation of microtubule nucleation mediated by γ-tubulin complexes
