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Lecture 10

CBIO 3400 Lecture Notes - Lecture 10: Rheb, Knockout Mouse, Sirolimus


Department
Cellular Biology
Course Code
CBIO 3400
Professor
Shen
Lecture
10

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CBIO 3400
Lecture 10
01/31/2019
Exam 1 material ends today**
mTOR (mammalian target of rapamycin)
Ser/Thr kinase (adds phosphate group to either serine or thr residues) with multiple
targets
Gets activated by mitogens and growth factors
o We want them to divide and growth which is why both parts get stimulated
Regulates cell growth and proliferation
If I tell you mTOR is regulated by a GTPase, what can you predict about this G-protein?
o It’s a G-protein, so we expect it to be regulated via GAP and Gef
G-protein regulation of mTOR
Rheb
o Monomeric G-protein that activates mTOR
TSC1/TSC2
o Act as a GAP for Rheb
Induce Rheb to hydrolyze GTP (goes from active to inactive state)
GEF for Rheb is unknown still
TSC1/TSC2 inhibited when growth factors bind receptors
o Can positively or negatively regulate this GAP
o TSC1/TSC2 get phosphorylated on the inactivation sites
mTOR Functions
mTOR regulates metabolism and activates:
o Translation
o Ribosome biogenesis
Make more proteins, you want to increase amount of ribosome in the
cytosol
o RNA polymerase III
RNA polymerase III can synthesize tRNA and rRNA
mTOR inhibits autophagy
Inhibiting mTOR increase the lifespan in model organisms.
mTOR and lifespan
mTOR knockout mice survive longer than control mice
% survival of mice, mice that have mTOR knocked out (nonfunctional copy) survival
longer of those who have wild type (normal) copy
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