Protein kinase CK2 both promotes robust proliferation and inhibits the proliferative fate in the C. elegans germ line.
Stem cells are capable of both self-renewal (proliferation) and differentiation. Determining the regulatory mechanisms controlling the balance between stem cell proliferation and differentiation is not only an important biological question, but also holds the key for using stem cells as therapeutic agents. The Caenorhabditis elegans germ line has emerged as a valuable model to study the molecular mechanisms controlling stem cell behavior. In this study, we describe a large-scale RNAi screen that identified kin-10, which encodes the β subunit of protein kinase CK2, as a novel factor regulating stem cell proliferation in the C. elegans germ line. While a loss of kin-10 in an otherwise wild-type background results in a decrease in the number of proliferative cells, loss of kin-10 in sensitized genetic backgrounds results in a germline tumor. Therefore, kin-10 is not only necessary for robust proliferation, it also inhibits the proliferative fate. We found that kin-10's regulatory role in inhibiting the proliferative fate is carried out through the CK2 holoenzyme, rather than through a holoenzyme-independent function, and that it functions downstream of GLP-1/Notch signaling. We propose that a loss of kin-10 leads to a defect in CK2 phosphorylation of its 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 the stem cell fate decision.
Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
Xin
X
Wang
Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
Pratyush
P
Gupta
Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
Jared
J
Fairbanks
Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4. Electronic address: dhansen@ucalgary.ca.
Dave
D
Hansen
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*
D000906:Antibodies; D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; C109286:fem-3-binding protein, C elegans; D047390:Casein Kinase II; C000590648:Kin-10 protein, C elegans
Germline development; Meiotic entry; Notch signaling; Proliferation; Protein kinase CK2; kin-10