lecture 3 Flashcards
how does UBL attach to proteins
covalently
describe the way in which UBLs are attached
carboxyl terminus plus the lysine side chain form a isopeptide bond by a condensation reaction.
what does the attachment of UBL do
1)control protein levels 2)changes in protein localisation 3)alter protein function 4)control gene transcription.
describe the cycle in which UBL reaches the target protein.
E1 charges UBL then transferred to E2. E3 ligases transfer the UBL to the target protein.E4 elongates the UBL chain.
what removes the UBL
deubiquitinases
what are the 2 DUB families
thiol proteases and metalloproteases
What is the role of E1 in Ub conjugation
UBA1 which is an E1 and UBA6 have specific E2 partners.
what E1 is found in FAT10ylation
UBA6
what is the function of E2 in Ub conjugation
has a UBC catalytic domain.
which two E2 are large
BIRC6 and UBE2O
in E2 what modulates the UBC activity and function
N and C terminal extensions
which two E3 ligases are known
28 HECT and 14 RBR
which two linkages are best described
K48 AND 63
what does DUB regulation promote
rescues of proteins from proteolytic degradation and restores function to modified proteins.
name 2 ubiquitin related cell surface proteins
EGFR and HER2
what transcription factor is related to ubiquitin regulated nuclear localisation
YAP factor is in macrophages. when bound to K63-Ub goes to nucleus because of inflammation.
what does YAP-K63-Ub activate
chemokine gene transcription which promotes atherosclerosis and plaque formation.
loss of which enzymes can impair DNA repair
E2 and E3
what are CDKs and what is there function
they are protein kinases and form CDK-cyclin complex that regulates cell cycle.
what transfers ubiquitin to cyclins
Skp Cullin F-box complex and APC/C
what is TP53 and what does it do
tumour suppressor protein. arrests apoptosis.
what regulates p53 levels
MDM2 which is E3 ligase
what is the structure of MDM2
can be homo or heterodimer. has a RING domain. catalytic residues.
what does AngII stimulate
phosphorylation of downstream mediators
what can excessive signalling lead to
cardiac remodelling
what controls signalling
PTEN
what does AngII promote
increases in UBA1 and enhanced ubiquitination of PTEN.
what is MuRF1 and what does it control
is a cardiac E3 ligase and controls Calcineurin A levels.
what is calcinerin A and what is it’s role
calcium dependant Ser/Thr protein phosphatase. regulates NFAT status and nuclear translocation.
what do MDM2 inhibitors compete for
p53 binding
what does targeting DUB specific substrate activity do
increase ubiquitination and degradation of client protiens.
what is PROTAC
