mTOR

Question 1

What type of science is the mTOR pathology

Answer 1

BOTTOM UP

Question 2

What is mTOR

Answer 2

known as a master regulator of cell signalling. the mechanistic target of rapamycin

Question 3

name some properties of rapamycin

Answer 3

antifungal
antitumour
immunosuppressant

Question 4

what does mTOR bind to to form a a gain of function complex

Answer 4

FKB12 (enzyme)

Question 5

what is FKB12

Answer 5

peptidyl-prolyl isomerase enzyme

Question 6

true or false mTOR has a highly conserved structure

Answer 6

true as it serves a very important function

Question 7

describe the structure of mTOR

Answer 7

20 heat repeats,2α linked by short loop
-FAT
-FRB
-Kianase NRD
-FACTC

Question 8

what is the function of the heat repeats?

Answer 8

bind to other proteins

Question 9

what is the function of the FAT region

Answer 9

are required for catalytic proteins of mTOR

Question 10

What is the function of FRB region

Answer 10

targeted by rapamycin FKBP12 COMPLEX

Question 11

What is the function of the kinase region

Answer 11

phosphorylate target proteins and is embedded in catalytic domain

Question 12

what is the function of the negative regulatory domain (NRD)

Answer 12

contains specific serine and threonine amino acids which are phosphorylated by other cellular kinases

Question 13

why is the phosphorylation site important

Answer 13

phosphorylation site is important for the regulation of mTOR activities

Question 14

what are the two multiprotein cellular complexes

Answer 14

mTOR 1 and mTOR 2

Question 15

What is the mechanism of action of rapamycin

Answer 15

prevents assembly of m TOR 1. but doesn’t affect mTOR 2 as it contains distinct proteins that can still bind to m TOR even in the presence of rapamycin

Question 16

what are the similarities between mTORC 1 and 2

Answer 16

• deptor
• mLST8
• mTOR

Question 17

what are the differences between mTORC 1 and 2

Answer 17

mTORC 1: pras40,raptor
mTORC 2: protor, siin 1, rictor

Question 18

what is the function of FKB12 in mTORC 1

Answer 18

disrupts the interaction between mTOR and raptor

Question 19

what is the function of mLST8

Answer 19

associated wit the catalytic domain of mTOR by stabilising kinase activation loop of mTOR

Question 20

if mLST8 is removed is mTOR still functional? (1)

Answer 20

yes

Question 21

what is the function of pras40 and deptor (1)

Answer 21

inhibitory subunits

Question 22

what is the function of a raptor (1)

Answer 22

facilitates the recruitment of different mTOR substrates which will later be phosphorylated by mTOR this is done by binding to specific protein motif

Question 23

Does raptor require subcellular localisation? (1)

Answer 23

yes

Question 24

what is the function of sin 1,protor and deptor (2)

Answer 24

regulatory proteins

Question 25

what is the function of rictor (2)

Answer 25

rapamycin-insensitive companion of mTOR. recruits substrates proteins for phosphorylation by mTOR

Question 26

what is the function of rapamycin FKB12 in mTORC2

Answer 26

doesn’t ‘t directly bind or inhibit mTORC 2 if the cell is exposed to the long treatment of rapamycin it will cause the inhibition of mTORC2 due to the inability of rapamycin-bound mTOR kinase to incorporate new mTOR2 complexes

Question 27

explain the role of mTORC1 in upstream regulation of mTOR Complexes

Answer 27

functions as a downstream mediator of several growth factor signalling pathway due to the pathway inhibiting a key -ve regulator of mTOR signalling tuberous sclerosis complex (TSC)

Question 28

mTORC 1 activation is controlled by

Answer 28

nutrient availability from food so activated after feeding to promote growth and energy storage in tissue

Question 29

is mTORC1 inhibited during fasting

Answer 29

yes to conserve limited energy

Question 30

what does upstream regulation of mTOR complexes do

Answer 30

regulates cellular growth and proliferation

Question 31

explain the activation of mTORC 1 by Rheb

Answer 31

TSC acts as GTPase GTPase-activating protein(GAP) for Rheb Directly binds and activates mTORC1

Question 32

What is TSC

Answer 32

tuberous sclerosis complex

Question 33

the Rheb GTPase

Answer 33

small Rheb GTPase continuously cycles in its inactive form GDP bound form and active GTP bound form and is regulated by the activity of GEF an GAD

Question 34

what is GAP

Answer 34

stands for GTPase-activating protein which activates GDP-bound (INACTIVE) form of GTPase.

Question 35

what is GEF

Answer 35

stands for Guanine nucleotide exchange factor which promotes active GTP bound form of protein

Question 36

where is rheb found

Answer 36

lysosome membrane

Question 37

describe the activation of mTORC1 by Rheb

Answer 37

growth factor signalling (such as insulin growth factor) leads to the phosphorylation of TSC which inhibits phosphorylation GAP activity causing Rheb to be activated by promoting rhebGTP so leads to activation of mTORC 1

Question 38

How do amino acids stimulate mTORC 1

Answer 38

-feeding leads to an increase in aa levels
- aa is sensed by RAG GTPase in mTORC1
- aa simulation converts RAG to active GTP bound state which means they can bind to raptor which stimulates mTORC formation at lysosome membrane
- raptor & mTORC1 in lysosomal membrane the RAG promote the association between mTOR and rheb once complex is formed it can be activated by rheb at cellular localisation

Question 39

what are RAG

Answer 39

Obligate-heterodimers made up of RAG A/B or RAG C/D

Question 40

describe the negative regulation of mTORC1 by AMPK

Answer 40

mTORC1 also responds to intracellular and environmental stressors which are incompatible with growth ex; low ATP levels. AMPK can directly regulate mTORC1 by phosphorylating the raptor at an inhibitory site. If cellular energy levels are down during glucose deprivation; the AMP: ATP ratio within the cell will change which activates AMP Kinase(inhibits mTORC1 directly by phosphorylating the TSC at the activation site which means rheb becomes inactive in its GDP-bound form before inactivating mTORC action/

Question 41

what is the regulation of mTORC2 activated by

Answer 41

insulin signalling by P13

Question 42

Describe how the regulation of mTORC2 is activated by insulin signalling by P13 kinase

Answer 42

in the absence of insulin, mTORC2 will be inactive once insulin binds to both activated P13 kinase and activated AKT can phosphorylate and activate mTORC2

Question 43

what is mTORC1 responsible for

Answer 43

regulating the balance between anabolism and catabolism in response to environmental conditions

Question 45

downstream signalling by mTORC1

Answer 45

mTORC1 activity will phosphorylate S6K causing it to be activated=> it then goes on to phosphorylate substrates and initiation factors that promote the formation and function of 5’ cap of mRNA