RRC ID 77279
Author Zhang H, Zhang Q, Gao G, Wang X, Wang T, Kong Z, Wang G, Zhang C, Wang Y, Peng G.
Title UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling.
Journal 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.
Volume 14(8)
Pages e1007583
Published 2018-8-1
DOI 10.1371/journal.pgen.1007583
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
Zebrafish UAS:GFP