mTORbeta splicing isoform promotes cell proliferation and tumorigenesis.
The mTOR (mammalian target of rapamycin) promotes growth in response to nutrients and growth factors and is deregulated in numerous pathologies, including cancer. The mechanisms by which mTOR senses and regulates energy metabolism and cell growth are relatively well understood, whereas the molecular events underlining how it mediates survival and proliferation remain to be elucidated. Here, we describe the existence of the mTOR splicing isoform, TOR beta, which, in contrast to the full-length protein (mTOR alpha), has the potential to regulate the G(1) phase of the cell cycle and to stimulate cell proliferation. mTOR beta is an active protein kinase that mediates downstream signaling through complexing with Rictor and Raptor proteins. Remarkably, overexpression of mTOR beta transforms immortal cells and is tumorigenic in nude mice and therefore could be a proto-oncogene.
Panasyuk
Ganna
G
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv-143, Ukraine.
Nemazanyy
Ivan
I
Zhyvoloup
Aleksander
A
Filonenko
Valeriy
V
Davies
Derek
D
Robson
Mathew
M
Pedley
R Barbara
RB
Waterfield
Michael
M
Gout
Ivan
I
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D000090063:Proto-Oncogene Mas; D012326:RNA Splicing; D058570:TOR Serine-Threonine Kinases
C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases