| RRC ID |
28901
|
| 著者 |
Lee KS, Wu Z, Song Y, Mitra SS, Feroze AH, Cheshier SH, Lu B.
|
| タイトル |
Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway.
|
| ジャーナル |
Genes Dev
|
| Abstract |
The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.
|
| 巻・号 |
27(24)
|
| ページ |
2642-7
|
| 公開日 |
2013-12-15
|
| DOI |
10.1101/gad.225169.113
|
| PII |
27/24/2642
|
| PMID |
24352421
|
| PMC |
PMC3877754
|
| MeSH |
Animals
Brain Neoplasms / physiopathology
Cell Line, Tumor
Cell Proliferation
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism
Gene Expression Regulation
Humans
Mechanistic Target of Rapamycin Complex 2
Microscopy, Electron, Transmission
Mitochondria / enzymology
Mitochondria / metabolism*
Mitochondria / ultrastructure
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism*
Mutation
Neoplastic Stem Cells / metabolism*
Protein Kinases / genetics
Protein Kinases / metabolism*
RNA Interference
Receptors, Notch / metabolism*
Signal Transduction*
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism*
|
| IF |
9.527
|
| 引用数 |
45
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
2286R-3 |
