Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 74, Issue 7, Pages 723-742Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0000000000000212
Keywords
Gamma-tubulin; Gamma-tubulin complex proteins; GCP2; GCP3; Glioma; Glioblastoma; Nucleolus
Categories
Funding
- Ministry of Education, Youth and Sports of the Czech Republic [LH12050]
- Ministry of Health of the Czech Republic [NT14467]
- Grant Agency of the Czech Republic [P302/12/1673]
- Academy of Sciences of the Czech Republic [M200521203PIPP]
- Technology Agency of the Czech Republic [TE01020118]
- Ministry of Industry and Trade of the Czech Republic [FR-TI3/588]
- Philadelphia Health Education Corporation (PHEC)
- St. Christopher's Hospital for Children Reunified Endowment [323256]
- [RVO 68378050]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available