Investigation of the role of Cyclin-dependent Kinase 5 in mediating bortezomib sensitivity in multiple myeloma.
Date
2014-05-26
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Abstract
Cyclin-dependent kinase 5 (Cdk5) was previously shown to mediate sensitivity of multiple myeloma cells to the proteasome inhibitor bortezomib. The mechanism by which this occurs was investigated. The idea that Cdk5 could promote the expression of the target of bortezomib PSMB5 via the transcription factor Nrf2 was first examined. However, contrary to published results, I did not find that PSMB5 expression is reduced following Cdk5 knockdown, and Nrf2 activity was also unchanged. Next, a synthetic lethal DNA repair defect from combined Cdk5 knockdown and bortezomib was explored. Both treatments produce an impaired DNA damage response. I show that Cdk5 can affect BRCA1 localization, Further investigation is required to fully characterize the role of Cdk5 in the DNA damage response. Bioinformatics supports the importance of Cdk5 in myeloma as we show that Patients with the highest expression of Cdk5 experience poorer survival following bortezomib treatment. Also, Cdk5 is upregulated in over 50% of all cancers.
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Keywords
Biology--Cell, Oncology
Citation
Levacque, Z. (2014). Investigation of the role of Cyclin-dependent Kinase 5 in mediating bortezomib sensitivity in multiple myeloma. (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26663