MTOT

Question 1

1. What does mTORC1 phosphorylate? What function does it have?
2. What does mTORC2 phosphorylate? What function does it have?
3. What is Hyper-activation of the mTOR signaling pathway associated with?

Answer 1

1. substrates including S6K, 4E-BP1 and SREBP to promote protein synthesis.
2. mTORC2 phosphorylates multiple AGC kinases including Akt, SGK and PKC to facilitate cell proliferation and survival.
3. It’s frequently observed in many types of human cancers.

Question 2

4. What are analog of rapamycin called?
5. Is rapamycin a good cancer treatment? Explain…
6. How does rapamycin affect the cell cycle?

Answer 2

4. Rapalogs
5. rapamycin treatment has displayed poor outcomes for most cancer types and severe side-effects in patients, which may be in part due to the insensitivity of mTORC2 to rapamycin, as well as the reactivation of the PI3K/Akt signaling upon mTORC1 inhibition to unleash the negative feedback loop.
6. rapamycin also leads to a G1-phase cell cycle arrest mediated in part by TGF-β signaling to promote cell survival. However, cells in S-phase undergo apoptosis.

Question 3

7. does inhibiting mTOR by rapamycin in S-phase lead to replication stress, which in turn results in apoptosis?
8. Is rapamycin cell-type/tissue specific?

Answer 3

7. If so, better clinical outcomes could be achieved using a combination of rapamycin with DNA replication inhibitors.
8. It seems that the effects of rapamycin are cell type or tissue context-dependent. Therefore, further investigation is required to uncover the molecular mechanisms underlying how rapamycin functions in different cancer types, which will provide the rationale and facilitate the optimization for the clinical application of rapamycin as an anti-cancer drug, alone or in combination with other agents to benefit more cancer patients.