RRC ID 45738
著者 Gupta P, Leahul L, Wang X, Wang C, Bakos B, Jasper K, Hansen D.
タイトル Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in the C. elegans germ line.
ジャーナル Development
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.
巻・号 142(2)
ページ 291-302
公開日 2015-1-15
DOI 10.1242/dev.115147
PII 142/2/291
PMID 25564623
PMC PMC6514403
MeSH Animals Blotting, Western Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism Cell Differentiation / physiology* Cell Proliferation / physiology* Computational Biology Germ Cells / growth & development* Germ Cells / metabolism Immunoprecipitation Proteasome Endopeptidase Complex / metabolism* RNA Interference Two-Hybrid System Techniques Ubiquitin-Protein Ligases / metabolism*
IF 5.611
引用数 12
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm1227