PUBLICATION
UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
- Authors
- Zhang, H., Zhang, Q., Gao, G., Wang, X., Wang, T., Kong, Z., Wang, G., Zhang, C., Wang, Y., Peng, G.
- ID
- ZDB-PUB-180807-8
- Date
- 2018
- Source
- PLoS Genetics 14: e1007583 (Journal)
- Registered Authors
- Peng, Gang, Zhang, Cuizhen, Zhang, Hefei
- Keywords
- none
- MeSH Terms
-
- 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
- PubMed
- 30080879 Full text @ PLoS Genet.
Citation
Zhang, H., Zhang, Q., Gao, G., Wang, X., Wang, T., Kong, Z., Wang, G., Zhang, C., Wang, Y., Peng, G. (2018) UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling. PLoS Genetics. 14:e1007583.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping