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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リソース情報 |
ショウジョウバエ |
|