Dev115147 291..302
نویسندگان
چکیده
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. Herewe focus on proteasome-mediated protein degradation as ameansof 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, asbeing involved in regulatingproliferative fate. RFP-1 binds toMRG-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 ofMRG-1 and a shift towards increased proliferation in sensitizedgenetic backgrounds. Likewise, reduction ofMRG-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.
منابع مشابه
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INTRODUCTION............................................................ 290 ACTION ON BACTERIA.................................................... 291 General Effects of Rifamycins In Vivo and In Vitro.............................. 291 Interaction of Rifamycins with DNA-Dependent RNA Polymerase (EC 2.7.7.6.) ..... ... 291 Characterization of RNA polymerase.........................................
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