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cancer > L10 > Flashcards

L10 Flashcards

1
Q

2 molecules that can phosphorylate ser473 on AKT

A

DNA-dependent protein kinase and mTORC2

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2
Q

what does activated AKT phosphorylate

A

BAD, FoxO

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3
Q

what happens when BAD is phosphorylated

A

it is prevented from promoting apoptosis

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4
Q

what kind of molecule is BAD

A

pro-apoptotic

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5
Q

2 places for BAD phosphorylation

A

Serine 136 and serine 112

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6
Q

what phosphorylates BAD serine 136

A

AKT

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7
Q

what phosphorylates BAD serine 112

A

PIM1, PIM2, PKA

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8
Q

what happens to bad once it is phosphorylated (what does it bind to)

A

14-3-3 => gets sequestered in cytoplasm and soaks up proteins like a scaffold protein

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9
Q

why is 14-3-3 called that

A

when they isolated it they used chromatography and gel electrophoresis - it was the numbers of the column and gel

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10
Q

what does BAD do when it’s active (ie. not phosphorylated)

A

it binds to anti-apoptotic molecule Bcl-XL

BAD displaces Bax, and therefore monomeric BAX will go make a Pore

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11
Q

what happens when Akt phosphorylates FoxO

A

it prevents FoxO from promoting apoptosis and cell cycle arrest

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12
Q

what does FoxO induce

A

FasL, and also P27 and P21 - these bind to cdks which inhibit cell cycle proliferation

FasL is a death causing hormone

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13
Q

what does FasL bind

A

FasR - triggers signalling cascade that promotes apoptosis

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14
Q

what does FoxO bind to once phosphorylated b y Akt

A

it leaves the nucleus and gets recognized by 14-3-3 => then gets sequestered in cytoplasm

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15
Q

does AKT activate mTORC1

A

yes but in a long-winded way

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16
Q

first thing AKT phosphorylates in the mTORC1 pathway

A

it inhibits TSc1 and TSC2 - these are tutor suppressors 0> it does this by phosphorylating TSC2

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17
Q

what does mTOR mean

A

mammalian target of rapamycin

18
Q

how do TSC1 and TSC2 affect mTOR

A

they inhibit mTOR

19
Q

what kind of molecule is AKT

A

serine threonine kinase

20
Q

what is another name for tsc2

A

tuberin

21
Q

another name for tsc1

A

hamartin

22
Q

how many residues does AKT phosphorylate on TSC2

A

2 in drosophila, at least 4 in humans

23
Q

what happens to TSC2 when act phosphorylates it

A

entire complex becomes unstable and is destroyed

24
Q

does the tsc complex directly interact with mTOR

A

no - it interacts with Rheb

25
Q

what kind of molecule is Rheb

A

small GTPase

26
Q

how does TSC2 interact with Rheb

A

TSC2 contains a gap domain that catalyzes conversion of Rheb-GTP into Rheb-GDP - so TSC2 inactivates Rheb

Rheb activates mTOR but not sure how

27
Q

what does mTOR phosphorylate

A

downstream targets S6K and 4EBP

28
Q

what cellular processes Does mTORC1 proomote

A

growth, proliferation, and increase in metabolism

29
Q

2 mTORC1 complex proteins that have negative effect on mTOR activity

A

Deptor and PRAS40

30
Q

2 mTORC complex proteins that have positive effect on mTOR activity

A

Raptor and GBL

31
Q

what are the 2 phosphorylations ties on mTOR

A

2448 and 2481

32
Q

how is 2481 phosphorylated

A

autophosphorylated

33
Q

how does AKT promote mTOR activity

A

phosphorylates PRAS49 at thr246

(also gets phosphorylated by MTORC1 and at 183 and 221)

PRAS40 then disengages and binds 14-3-3

34
Q

so what are the 2 overall ways that act promotes mTOR activity

A

inhibition of TSC2 and phosphorylation of PRAS40

35
Q

how does Rapamycin inhibit MTORC1

A

directly binds to mTOR and prevents its interaction with Raptor

36
Q

is mTORC2 sensitive to rapamycin

A

no

37
Q

what does EIF4E do

A

bound to m7GTP and stabilizes mRNA

38
Q

what does 4EBP do

A

binds to eIF4E and prevents pre-initiation complex proteins from binding

39
Q

how does mTORC affect 4EBP

A

phosphorylates it, and then it cant bind to eIF4E -> it then dissociates

40
Q

what happens when 4EBP dissociates -

A

EIF4G and A come to recruit other factors and initiation complex

cancer (10 decks)

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