The Role of Protein Kinase CK2 in the Proliferative Fate vs. Differentiation Decision in the C. elegans Germ Line

Wang, Xin

The Role of Protein Kinase CK2 in the Proliferative Fate vs. Differentiation Decision in the C. elegans Germ Line

atmire.migration.oldid	1611
dc.contributor.advisor	Hansen, David
dc.contributor.author	Wang, Xin
dc.date.accessioned	2013-10-17T22:24:04Z
dc.date.available	2014-03-15T07:00:14Z
dc.date.issued	2013-10-17
dc.date.submitted	2013	en
dc.description.abstract	Stem cells are capable of self-renewal (proliferation) and differentiation. Proliferation generates daughter cells with virtually the same properties as the parental cell, whereas differentiation produces specialized cell types used in tissue formation. Determining the regulatory mechanisms controlling stem cell proliferation and differentiation is not only an important biological question, but also holds the key for using stem cells as a therapeutic agent. The Caenorhabditis elegans germ line has emerged as an invaluable model to study the molecular genetic code dictating stem cell activity. In this thesis, kin-10, which encodes the β subunit of protein kinase CK2, has been identified as a novel factor regulating stem cell proliferation in the C. elegans germ line. In an effort to determine how kin-10 functions within the regulatory pathway, genetic analysis was performed with known regulatory components. A loss of kin-10 is able to enhance the over-proliferation phenotype of elevated GLP-1/Notch signaling, as well as result in a synthetic tumorous phenotype when the GLD-2 pathway is defective. Further, the synthetic tumorous phenotype appears to be epistatic to glp-1, indicating that kin-10 functions downstream of GLP-1/Notch signaling, likely in the GLD-1 pathway to inhibit proliferation and/or promote meiotic entry. Additional analysis also revealed that kin-10’s regulatory role in stem cell proliferation is likely carried out through the CK2 holoenzyme. I propose that a loss of kin-10 leads to a defect in CK2 phosphorylation of its yet-to-be identified downstream targets, resulting in abnormal activity of target protein(s) that are involved in the proliferative fate vs. differentiation decision. This eventually causes a shift towards the proliferative fate in stem cell fate decision.	en_US
dc.identifier.citation	Wang, X. (2013). The Role of Protein Kinase CK2 in the Proliferative Fate vs. Differentiation Decision in the C. elegans Germ Line (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28350	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/28350
dc.identifier.uri	http://hdl.handle.net/11023/1151
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	Genetics
dc.subject	Biology--Molecular
dc.subject.classification	Stem Cells	en_US
dc.subject.classification	Proliferation	en_US
dc.subject.classification	meiotic differentiation	en_US
dc.subject.classification	C. elegans	en_US
dc.subject.classification	germline development	en_US
dc.subject.classification	kin-10	en_US
dc.subject.classification	protein kinase CK2	en_US
dc.subject.classification	Notch signaling	en_US
dc.subject.classification	Tumor	en_US
dc.title	The Role of Protein Kinase CK2 in the Proliferative Fate vs. Differentiation Decision in the C. elegans Germ Line
dc.type	doctoral thesis
thesis.degree.discipline	Biological Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.item.requestcopy	true