Lecture 3: The TOR Pathway Flashcards
Which protein kinase is the central controller of cell growth and aging?
mTOR (Mammalian Target of Rapamycin)
What is the mTOR protein kinase sensitive to?
nutrients
Does mTOR stimulate cell growth or proliferation?
Both
What are the two functions of mTOR?
1) Stimulate translation (part of growth)
2) Stimulate proliferation
What can AKT do to TSC1/2 in the TOR pathway?
It is an oncogene that inhibits the TSC1/2 tumor suppressor
What is the effect on mTOR of AKT inhibiting TSC1/2?
mTOR is stimulated by the Rheb oncogene (since Rheb is not inhibited by TSC1/2), and because of this, the cell manufactures more ribosomes (increasing cell growth and proliferation)
What is the effect on mTOR if AKT does not inhibit TSC1/2?
TSC1/2 will inhibit the Rheb oncogene, thereby inhibiting mTOR and stopping ribosome production and cell proliferation
What is rapamycin and what is it used for?
Rapamycin is from a fungus. It is an immune suppressor (causes B and T cells to plummet), and it is used most often in transplant patients
What is the immune suppressing drug that inhibits TOR activity?
Rapamycin
What does effect does active TSC1/2 have on ribosome production? Why?
It slows it down; it is a tumor suppressor that inhibits Rheb and, thereby, TOR
Which condition is similar to neurofibromatosis in that people who carry a mutation in the germline usually get the condition (though it is usually not highly malignant) and people who don’t, don’t? What tumor suppressor is affected?
tuberous sclerosis; TSC1 and TSC2
Does active AKT increase or decrease ribosome production? Why
Increases it; AKT inhibits the tumor suppressors TSC 1 and 2, thereby preventing the deactivation of Rheb, which stimulates mTOR, which stimulates ribosome production.