lecture 3

Question 1

how does UBL attach to proteins

Answer 1

covalently

Question 2

describe the way in which UBLs are attached

Answer 2

carboxyl terminus plus the lysine side chain form a isopeptide bond by a condensation reaction.

Question 3

what does the attachment of UBL do

Answer 3

1)control protein levels 2)changes in protein localisation 3)alter protein function 4)control gene transcription.

Question 4

describe the cycle in which UBL reaches the target protein.

Answer 4

E1 charges UBL then transferred to E2. E3 ligases transfer the UBL to the target protein.E4 elongates the UBL chain.

Question 5

what removes the UBL

Answer 5

deubiquitinases

Question 6

what are the 2 DUB families

Answer 6

thiol proteases and metalloproteases

Question 7

What is the role of E1 in Ub conjugation

Answer 7

UBA1 which is an E1 and UBA6 have specific E2 partners.

Question 8

what E1 is found in FAT10ylation

Answer 8

UBA6

Question 9

what is the function of E2 in Ub conjugation

Answer 9

has a UBC catalytic domain.

Question 10

which two E2 are large

Answer 10

BIRC6 and UBE2O

Question 11

in E2 what modulates the UBC activity and function

Answer 11

N and C terminal extensions

Question 12

which two E3 ligases are known

Answer 12

28 HECT and 14 RBR

Question 13

which two linkages are best described

Answer 13

K48 AND 63

Question 14

what does DUB regulation promote

Answer 14

rescues of proteins from proteolytic degradation and restores function to modified proteins.

Question 15

name 2 ubiquitin related cell surface proteins

Answer 15

EGFR and HER2

Question 16

what transcription factor is related to ubiquitin regulated nuclear localisation

Answer 16

YAP factor is in macrophages. when bound to K63-Ub goes to nucleus because of inflammation.

Question 17

what does YAP-K63-Ub activate

Answer 17

chemokine gene transcription which promotes atherosclerosis and plaque formation.

Question 18

loss of which enzymes can impair DNA repair

Answer 18

E2 and E3

Question 19

what are CDKs and what is there function

Answer 19

they are protein kinases and form CDK-cyclin complex that regulates cell cycle.

Question 20

what transfers ubiquitin to cyclins

Answer 20

Skp Cullin F-box complex and APC/C

Question 21

what is TP53 and what does it do

Answer 21

tumour suppressor protein. arrests apoptosis.

Question 22

what regulates p53 levels

Answer 22

MDM2 which is E3 ligase

Question 23

what is the structure of MDM2

Answer 23

can be homo or heterodimer. has a RING domain. catalytic residues.

Question 24

what does AngII stimulate

Answer 24

phosphorylation of downstream mediators

Question 25

what can excessive signalling lead to

Answer 25

cardiac remodelling

Question 26

what controls signalling

Answer 26

PTEN

Question 27

what does AngII promote

Answer 27

increases in UBA1 and enhanced ubiquitination of PTEN.

Question 28

what is MuRF1 and what does it control

Answer 28

is a cardiac E3 ligase and controls Calcineurin A levels.

Question 29

what is calcinerin A and what is it's role

Answer 29

calcium dependant Ser/Thr protein phosphatase. regulates NFAT status and nuclear translocation.

Question 30

what do MDM2 inhibitors compete for

Answer 30

p53 binding

Question 31

what does targeting DUB specific substrate activity do

Answer 31

increase ubiquitination and degradation of client protiens.

Question 32

what is PROTAC