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

Date
2013-10-17
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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.
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Keywords
Biology--Cell, Genetics, Biology--Molecular
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