Tumor Suppressor function of the deubiquitinating enzyme BAP1 and its substrate gamma-tubulin In regulation of cell cycle and genome stability
Författare
Summary, in English
g-Tubulin is a member of the tubulin family that is required for interphase αβ-tubulin nucleation, spindle formation and centrosomal duplication. The cell cycle is a closely controlled process, involving multiple components with regulation on several levels. The findings from our studies suggest that at the G1/S-phase transition, when retinoblastoma protein (RB) releases E2 promoter binding factors (E2Fs), g-tubulin associates with and captures E2F to ensure a transient transcription of genes necessary for S-phase entry. In addition, we found that the g-tubulin deubiquitination enzyme, BRCA1 Associated Protein 1 (BAP1), was downregulated in metastatic adenocarcinoma breast cell lines compared to non-cancerous human breast epithelial cells. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Rescue experiments involving expression of BAP1 reduced ubiquitination of g-tubulin and prevented mitotic defects. Furthermore, we found that the tumour suppressor function of BAP1 in neuroblastoma is mediated through the arrest of cells in S phase, and further, it promoted cell death. In conclusion, our studies define important functions of g-tubulin and BAP1 in the regulation of the cell cycle and proper segregation of the chromosomes.
Avdelning/ar
- Avdelningen för translationell cancerforskning
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2015
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2015:67
Fulltext
Dokumenttyp
Doktorsavhandling
Förlag
Division of Translational Cancer Research
Ämne
- Cancer and Oncology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-7619-146-0
Försvarsdatum
27 maj 2015
Försvarstid
09:00
Försvarsplats
Medicon village, Building 302 Lecture Hall, Lund
Opponent
- Jeffrey Parvin (Professor)