| RRC ID |
77279
|
| 著者 |
Zhang H, Zhang Q, Gao G, Wang X, Wang T, Kong Z, Wang G, Zhang C, Wang Y, Peng G.
|
| タイトル |
UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish. Lastly, UBTOR depletion promotes tumor growth and mTOR signaling in a xenograft mouse model. Together, our results demonstrate how UBTOR regulates cell growth and neoplasia via mTOR signaling.
|
| 巻・号 |
14(8)
|
| ページ |
e1007583
|
| 公開日 |
2018-8-1
|
| DOI |
10.1371/journal.pgen.1007583
|
| PII |
PGENETICS-D-17-02181
|
| PMID |
30080879
|
| PMC |
PMC6095612
|
| MeSH |
Animals
Cell Line, Tumor
Cell Proliferation / genetics*
Chromosome Mapping
Female
Gene Deletion
Gene Expression Regulation*
HEK293 Cells
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neuronal Outgrowth / genetics*
PC12 Cells
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Signal Transduction
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism*
Xenograft Model Antitumor Assays
Zebrafish / genetics
Zebrafish / metabolism
|
| IF |
5.175
|
| リソース情報 |
| ゼブラフィッシュ |
UAS:GFP |
