Investigating the role of nuclear BNIP3 in regulation of cellular proliferation
| dc.contributor.author | Singh, Amandeep | |
| dc.contributor.examiningcommittee | Werbowetski-Ogilvie, Tamra (Biochemistry and Medical Genetics) Katyal, Sachin (Pharmacology and Therapeutics) | en_US |
| dc.contributor.supervisor | Gibson, Spencer (Biochemistry and Medical Genetics) | en_US |
| dc.date.accessioned | 2019-01-08T15:11:03Z | |
| dc.date.available | 2019-01-08T15:11:03Z | |
| dc.date.issued | 2018 | en_US |
| dc.date.submitted | 2018-12-20T01:06:03Z | en |
| dc.degree.discipline | Biochemistry and Medical Genetics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | BNIP3 is a member of BCL-2 family of cell death regulating proteins. When overexpressed in the cytoplasm under stress conditions such as hypoxia, BNIP3 localizes to the mitochondria and promotes cell death through mitochondrial dysfunction. Moreover, cytoplasmic (and mitochondrial) BNIP3 has also been shown to promote autophagy and autophagic cell death. However, when expressed in the nucleus, BNIP3 promotes cell survival by inhibiting transcription of certain cell death proteins. Interestingly, Bnip3-knockout mice show increased cellularity in the brain. Cell proliferation studies on MEF, primary mouse astrocytes and HEK293 cells confirmed that cells lacking BNIP3 are more proliferative than cells expressing nuclear BNIP3, indicating a novel role of nuclear BNIP3 in regulating cell proliferation. Furthermore, cells lacking BNIP3 also show increased activation of RAS-MAPK cell proliferation pathway, as well as increased expression of cell cycle proteins, Ki67 and Cyclin D1. Investigations into the mechanism through which BNIP3 may affect proliferation identified three target genes, however their expression differences between cells expressing or lacking BNIP3 were inconclusive. In summary, nuclear expression of BNIP3 plays a role in repressing cell proliferation. | en_US |
| dc.description.note | February 2019 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/33642 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | BNIP3 | en_US |
| dc.subject | Proliferation | en_US |
| dc.title | Investigating the role of nuclear BNIP3 in regulation of cellular proliferation | en_US |
| dc.type | master thesis | en_US |