RRC ID 48861
著者 Wu YC, Lee KS, Song Y, Gehrke S, Lu B.
タイトル The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.
ジャーナル PLoS Genet
Abstract Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology.
巻・号 13(5)
ページ e1006785
公開日 2017-5-1
DOI 10.1371/journal.pgen.1006785
PII PGENETICS-D-16-02803
PMID 28520736
PMC PMC5453605
MeSH Animals Brain / cytology Brain / metabolism* Cell Differentiation Cell Growth Processes Drosophila / cytology Drosophila / genetics* Drosophila / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Feedback, Physiological Juvenile Hormones / genetics* Juvenile Hormones / metabolism MicroRNAs / genetics* Neoplastic Stem Cells / cytology Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / physiology Neural Stem Cells / cytology Neural Stem Cells / metabolism Neural Stem Cells / physiology Receptors, Notch / genetics Receptors, Notch / metabolism* Signal Transduction
IF 5.175
引用数 7
WOS 分野 GENETICS & HEREDITY
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