lecture 3 Flashcards

1
Q

how does UBL attach to proteins

A

covalently

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2
Q

describe the way in which UBLs are attached

A

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

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3
Q

what does the attachment of UBL do

A

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

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4
Q

describe the cycle in which UBL reaches the target protein.

A

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

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5
Q

what removes the UBL

A

deubiquitinases

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6
Q

what are the 2 DUB families

A

thiol proteases and metalloproteases

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7
Q

What is the role of E1 in Ub conjugation

A

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

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8
Q

what E1 is found in FAT10ylation

A

UBA6

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9
Q

what is the function of E2 in Ub conjugation

A

has a UBC catalytic domain.

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10
Q

which two E2 are large

A

BIRC6 and UBE2O

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11
Q

in E2 what modulates the UBC activity and function

A

N and C terminal extensions

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12
Q

which two E3 ligases are known

A

28 HECT and 14 RBR

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13
Q

which two linkages are best described

A

K48 AND 63

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14
Q

what does DUB regulation promote

A

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

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15
Q

name 2 ubiquitin related cell surface proteins

A

EGFR and HER2

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16
Q

what transcription factor is related to ubiquitin regulated nuclear localisation

A

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

17
Q

what does YAP-K63-Ub activate

A

chemokine gene transcription which promotes atherosclerosis and plaque formation.

18
Q

loss of which enzymes can impair DNA repair

A

E2 and E3

19
Q

what are CDKs and what is there function

A

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

20
Q

what transfers ubiquitin to cyclins

A

Skp Cullin F-box complex and APC/C

21
Q

what is TP53 and what does it do

A

tumour suppressor protein. arrests apoptosis.

22
Q

what regulates p53 levels

A

MDM2 which is E3 ligase

23
Q

what is the structure of MDM2

A

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

24
Q

what does AngII stimulate

A

phosphorylation of downstream mediators

25
Q

what can excessive signalling lead to

A

cardiac remodelling

26
Q

what controls signalling

A

PTEN

27
Q

what does AngII promote

A

increases in UBA1 and enhanced ubiquitination of PTEN.

28
Q

what is MuRF1 and what does it control

A

is a cardiac E3 ligase and controls Calcineurin A levels.

29
Q

what is calcinerin A and what is it’s role

A

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

30
Q

what do MDM2 inhibitors compete for

A

p53 binding

31
Q

what does targeting DUB specific substrate activity do

A

increase ubiquitination and degradation of client protiens.

32
Q

what is PROTAC

A