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cancer > L15 > Flashcards

L15 Flashcards

1
Q

what is AP1

A

dimeric transcription factor composed of members of Jun and For families

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2
Q

what are June nd Fos

A

bZip factors

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3
Q

what do bZip factors do

A

dimerize through a leucine zipper motif and bind DNA through adjacent Basic region

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4
Q

why is the DNA binding subunit of LZ called basic region

A

because DNA binding domain has a lot of lysine and arginine, which are positively charged with lots of amine groups

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5
Q

can c-Jun form homodimers or heterodimers

A

both

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6
Q

can c-Fos form homodimers or heterodimers

A

only heterodimers

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7
Q

what controls c-Jun activity

A

phosphorylation/dephosphorylation

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8
Q

is c-Jun phosphorylated or not in unstimulated cells

A

phosphorylated on several set/thr residues in proximity of basic region

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9
Q

what happens when c-Jun is phosphorylatied

A

inhibition of DNA binding

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10
Q

why does phosphorylated c-Jun inhibit DNA binding

A

because the basic region is the region of DNA binding, and the phosphorylation is very close to it, so it interferes

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11
Q

is c-Jun phosphorylated or not in stimulated cells

A

ALSO YES - DIFFERENT SPOT

it’s phosphorylated in trans-activation domain

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12
Q

what molecule phosphorylates c-Jun

A

Erk and Jnk

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13
Q

what mediates phosphorylation near c-jun basic region

A

CKII and GSK3beta

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14
Q

what mediates phosphorylation in the activation domain of c-jun

A

JNK (and ERK)

this happens at docking domain

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15
Q

what are the 3 domains of c-jun

A

LLLL (Leucine wiper)
Trans-activation domain (TAD)
D (docking domain_
B (basic domain)

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16
Q

is c-jun -/- lethal

A

yes - embryonic lethal

17
Q

what kind of mitogenic response gene is c-fos

A

‘early immediate gene’

undetectable in quiescent cells and then transiently and abruptly inducible in response to mitogenic stimulations

18
Q

what is the most potent form of an AP-1 transcription factor

A

c-jun c-fos heterodimer

19
Q

what consensus sequence does c-jun c-fos bind to

A

TGACTCA

20
Q

what sorts of pathways does c-jun and c-fos regulate

A

cell cycle regulation, apoptosis, angiogenesis, metastasis

21
Q

4 blocks of evidence that AP-1 plays a role in oncogenesis

A
  1. AP-1 activity is elevated in cells transformed by RTK and NRTK
  2. expression of a dominant negative mutant of c-Jun (designated TAM67) blocks transformation by v-src and activated Ha-Ras
  3. MEFs nullizygous for c-jun cant be transformed in vitro by v-src or Ha-Ras
  4. c-jun -/- MEFs with v-src or activated Ha-Ras gene form tutors in mice with long delay
22
Q

AP-1 reason 1 AP-1 activity is elevated in cells transformed by RTK and NRTK

A

induced AP1 activity means this is downstream target

23
Q

AP-1 reason 2: expression of dominant negative c-Jun

A

if you engineer TAM67 to have no D or TAD, it will now bind c-jun because it’s ineffective and inactivated

cancer (10 decks)

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