Investigation of the role of Cyclin-dependent Kinase 5 in mediating bortezomib sensitivity in multiple myeloma.
| atmire.migration.oldid | 2196 | |
| dc.contributor.advisor | Lee, Ki-Young | |
| dc.contributor.author | Levacque, Zachary | |
| dc.date.accessioned | 2014-05-26T22:59:12Z | |
| dc.date.available | 2014-11-17T08:00:30Z | |
| dc.date.issued | 2014-05-26 | |
| dc.date.submitted | 2014 | en |
| dc.description.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. | en_US |
| dc.identifier.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 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/26663 | |
| dc.identifier.uri | http://hdl.handle.net/11023/1561 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Biology--Cell | |
| dc.subject | Oncology | |
| dc.title | Investigation of the role of Cyclin-dependent Kinase 5 in mediating bortezomib sensitivity in multiple myeloma. | |
| dc.type | master thesis | |
| thesis.degree.discipline | Medical Science | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.item.requestcopy | true |