title: Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in the C. elegans germ line.
abstract: The level of stem cell proliferation must be tightly controlled for proper development and tissue homeostasis. Multiple levels of gene regulation are often employed to regulate stem cell proliferation to ensure that the amount of proliferation is aligned with the needs of the tissue. Here we focus on proteasome-mediated protein degradation as a means of regulating the activities of proteins involved in controlling the stem cell proliferative fate in the C. elegans germ line. We identify five potential E3 ubiquitin ligases, including the RFP-1 RING finger protein, as being involved in regulating proliferative fate. RFP-1 binds to MRG-1, a homologue of the mammalian chromodomain-containing protein MRG15 (MORF4L1), which has been implicated in promoting the proliferation of neural precursor cells. We find that C. elegans with reduced proteasome activity, or that lack RFP-1 expression, have increased levels of MRG-1 and a shift towards increased proliferation in sensitized genetic backgrounds. Likewise, reduction of MRG-1 partially suppresses stem cell overproliferation. MRG-1 levels are controlled independently of the spatially regulated GLP-1/Notch signalling pathway, which is the primary signal controlling the extent of stem cell proliferation in the C. elegans germ line. We propose a model in which MRG-1 levels are controlled, at least in part, by the proteasome, and that the levels of MRG-1 set a threshold upon which other spatially regulated factors act in order to control the balance between the proliferative fate and differentiation in the C. elegans germ line.
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Pratyush
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Leahul
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Chris
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Brendan
authors.initials: B
authors.lastname: Bakos
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Katie
authors.initials: K
authors.lastname: Jasper
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive, Calgary, Alberta, Canada T2N 1N4 dhansen@ucalgary.ca.
authors.forename: Dave
authors.initials: D
authors.lastname: Hansen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D019295:Computational Biology; D005854:Germ Cells / Q000254:growth & development* / Q000378:metabolism; D047468:Immunoprecipitation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D034622:RNA Interference; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C470832:MRG-1 protein, C elegans; C482969:RING finger protein 1, C elegans; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Caenorhabditis elegans; E3 ubiquitin ligase; MRG-1; Proteasomal degradation; RFP-1; Stem cell proliferative fate; Substrate recognition subunit