RRC ID 45876
Author Wang X, Gupta P, Fairbanks J, Hansen D.
Title Protein kinase CK2 both promotes robust proliferation and inhibits the proliferative fate in the C. elegans germ line.
Journal Dev Biol
Abstract 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.
Volume 392(1)
Pages 26-41
Published 2014-8-1
DOI 10.1016/j.ydbio.2014.05.002
PII S0012-1606(14)00246-2
PMID 24824786
MeSH Amino Acid Sequence Animals Antibodies / immunology Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Casein Kinase II / genetics Casein Kinase II / metabolism* Cell Differentiation / genetics* Cell Proliferation* Germ Cells / cytology* Germ Cells / metabolism Phosphorylation RNA Interference RNA, Small Interfering RNA-Binding Proteins / genetics Receptors, Notch / genetics Receptors, Notch / metabolism Sequence Alignment Signal Transduction / genetics Stem Cells / metabolism*
IF 2.896
Times Cited 7
C.elegans tm1283