Pathways (NF-kB, HIF, JAK/STAT, MAPK cascade, P53 )

Question 1

NF-kB

Answer 1

is a dimer found in almost all animal cells, which regulates inflammation

Question 2

what does activation of NF-kB cause

Answer 2

transcription of anti-oxidant proteins (SOD), NADPH oxidase, COX-2 and iNOS

Question 3

what is NF-kB induced by

Answer 3

TNF-alpha, ROS, cocaine, viral and bacterial antigens

Question 4

NF-kB pathway

Answer 4

1) signal attaches to the receptor
2) activating IKK
3) IKK phosphorylates IKBalpha (which is in complex with NF-kB)
4) Once three phosphates added to IKBalpha, it detaches from NF-kB
5) NF-kB translates to the nucleus
6) activating genes which mediate inflammation

Question 5

NF-kB activates genes genes involved in

Answer 5

cell growth, survival, migration and angiogenesis

Question 6

JAK/STAT is involved in processes such as

Answer 6

immunity, cell division, cell death and tumour formation

Question 7

JAK/STAT receptor lacks

Answer 7

intrinsic tyrosine oatvity- activates janus kinase (cytosolic kinase receptor

Question 8

target genes for JAK/STAT

Answer 8

-MYC (porto-oncogenes)
-P21
-cytokines
-iNOS
SOC (suppressor of cytokine signaling)

Question 9

JAK/STAT can work to

Answer 9

suppress cytokine signalling via SOC

Question 10

JAK/STAT pathway

Answer 10

1) ligand binds to receptor (EPO)
2) receptor dimerises (confomational change)
3) JAKs move closer together and phosphorylate the receptor
4) phosphorylated receptor recruits the TF STAT
5) Receptor phosphorylates STAT
6) phosphorylated STAT dislocates from the recwproe and dimerises via phosphotyrosine
7) STAT dimer is a TF
8) translocates to the nucleus and activates transcription

Question 11

HIF is a

Answer 11

TF

Question 12

in hypoxic conditions

Answer 12

HIF induces transcription causing angiongensis- to supply tissue with more oxygen

Question 13

HIF plays a central role in

Answer 13

regulate of human metabolism

Question 14

HIF causes an increase in

Answer 14

anaerobic enzymes

Question 15

Normoxia

Answer 15

normal oxygen

-HIF degraded by hydroxylation

Question 16

Hypoxia

Answer 16

low oxygen

• HIF not degraded
• angiogensis

Question 17

Normoxia and HIF pathway

Answer 17

1) no shortage of O2 for proxylhydroxylate
2) HIF is hydroxylated
3) this attract E3 Ubiquitin ligase
4) HIF moves to proteasome and is degraded- therefore cannot cause transcription in the nucleus

Question 18

Hypoxia and HIF pathway

Answer 18

1) shortage of oxygen for proxy-hydroxylate
2) therefore HIF isn’t hydroxylated
3) E3-UL is not attracted to HIF- no ubiquitination
4) HIF translocates to the nucleus
5) HIFalpha and HIFbeta forms
6) proteins transcribed which help regulate hypoxia

Question 19

MAPK cascade stands for

Answer 19

mitogen activated protein kinases

Question 20

MAPK can be

Answer 20

initiated by MANY PATHWAYS

Question 21

what receptor does MAPK use

Answer 21

Tyrosine kinase

Question 22

overall affect of MAPK cascade

Answer 22

cell survival and proliferation

Question 23

MAPK cascade pathway

Answer 23

1) mitogen binds to RTK
2) receptor dimerzes
3) TK domain autophosphorylates
4) when phosphorylated the receptor attracts proteins with a SH2 domain (Grb2)
5) Grb2 is phosphorylated
6) sos which is attached to Grb2 is activated and phosphorylates RAS
7) RAS binds kinase RAF and activates via phosphorylation
8) MEK and ERK also phosphorylated by posh
9) ERk-P translates to the nucleus and acts as a TF
10) genes involving cell proliferation and survival

Question 24

overall the MAPK cascade causes

Answer 24

cell proliferation and survival

Question 25

order of MAPK cascade

Answer 25

1) Grb2 phos 2) SOS activation 3) phosphorylation of RAS by SOS 4) RAS activates RAF 5) RAF activates MEk 6) MEK activates ERK 7) ERK= TF

Question 26

RAS..

Answer 26

RAF, MEK, ERK

Question 27

P53 known as

Answer 27

the guardian of the genome

Question 28

P53 is a

Answer 28

tumour suppressor TF

Question 29

what does p53 regulate

Answer 29

inhibits cell cycle, G1/S and G2/M

Question 30

MDM2

Answer 30

E3 ubiquitin ligase

Question 31

how doe P53 inhibit cell cycle

Answer 31

stops cells from progressing when the cell is damaged or it will trying repair DNA

Question 32

P53 in a normal cell

Answer 32

1) E3 ubiquity ligase (MDM2) ubiqutinates P53 | 2) sent for proteasomal degradation

Question 33

normal cells will have ........ P53 expressed

Answer 33

very little- meaning mitosis can occur

Question 34

P53 in cellular stress

Answer 34

1) cell damage/DNA damage, hypoxia- activates oncogene 2) ATM kinase activated 3) ATM-K phosphorylates CHK1/2 kinase which phosphorylates P53 4) when phosphorylated P53 is unbound to MDM2 (which would usually send it to the proteasome) 5) P53 translocates to the nucleus to act as a TF 6) Apoptosis and DNA repair

Question 35

which genes do P53 transcribe

Answer 35

genes which cause apoptosis and DNA repair