- •Sensing the microbial universe
- •The toll receptor in Drosophila
- •Lipopolysaccharides: shield and signal
- •Signalling through the TLR4 receptor
- •The TIRAP/MyD88 pathway
- •From TRAF6 to activation of IRF-3
- •The TRAM, TRIF pathway
- •The IRF family of transcription factors
- •Negative feedback control of the TLR4 pathway
- •Some consequences of TLR4-induced gene transcription
- •Essay: ubiquitylation and SUMOylation
- •Ubiquitylation
- •Ubiquitylation: a process involving three activities (but not necessarily three proteins)
- •63K or 48K conjugation
- •Two classes of E3-ubiquitin ligases
- •Ubiquitin-binding proteins
- •SUMO and sumoylation
- •Essay: the proteasome complex
- •The proteasome
- •20S particle
- •Proteasome activator (PA) subunits
- •List of abbreviations
- •References
Signal Transduction
FIG 15.18 Activation mechanism of the 20S proteasome.
(a) Entry into the catalytic chamber is blocked by the -subunits that form the lining of the antechamber of the 20S particle. (b) Binding of the activating particle (red) changes
their conformation, opening the entry pore. In this way selectivity of protein degradation is assured because only capped 20S particles are accessible to substrate (1fnt,89 1ryp87).
Proteasome activator (PA) subunits
The regulatory PA700 subunit is composed of a minimum of 20 proteins, referred to as Rpn and Rpt.88 Together they organize (1) the fixation of substrate (with the help of an adaptor), (2) unfolding and transport of the polypeptide chain towards the proteasome interior,90 (3) removal of the ubiquitin chains, which are then recycled, and (4) the opening of the entry pore of the proteasome 20S particle (Figure 15.18).87,89 The composition of PA28 is less clear.
List of abbreviations
Abbreviation |
Full name/description |
SwissProt |
Other names/OMIM |
|
|
entry |
|
|
|
|
|
ATF2 |
activating transcription factor-2 |
P15336 |
CRE binding protein |
|
|
|
(CRE-BP1) |
|
|
|
|
cactus |
|
Q03017 |
|
|
|
|
|
Cbl |
casitas B-lineage lymphoma proto-oncogene |
P22681 |
|
|
|
|
|
CBP |
CREB binding protein |
Q92793 |
|
|
|
|
|
CD14 |
cluster of differentiation-14 |
P08571 |
|
|
|
|
|
cJun |
avian sarcoma virus 17 oncogene homologue |
P05412 |
|
|
(junana 17 in Japanese) |
|
|
|
|
|
|
CUE |
coupling of ubiquitin conjugation to endoplasmic |
|
ubiquitin binding |
|
reticulum degradation |
|
domain |
|
|
|
|
Continued
474
The Toll-like Receptor 4 and Signalling through Ubiquitylation
Abbreviation |
Full name/description |
SwissProt |
Other names/OMIM |
|
|
entry |
|
|
|
|
|
dorsal |
|
P15330 |
|
|
|
|
|
HECT |
homologous to E6AP C-terminus |
|
|
|
|
|
|
hHR23a |
human homologue of radiation repair protein 23a |
P54725 |
RAD23A |
|
|
|
|
I B |
inhibitor of NF- B type alpha |
P25963 |
|
|
|
|
|
IKK- |
Inhibitor of NF- B alpha (IkB)-kinase type alpha |
|
|
|
|
|
|
IKK- |
inhibitor of NF- B alpha (IkB)-kinase type beta |
O14920 |
|
|
|
|
|
IKK- |
Inhibitor of NF- B alpha (IkB)- kinase type epsilon |
Q14164 |
|
|
|
|
|
IL-1R1 |
interleukin-1 alpha receptor-1 |
P14778 |
|
|
|
|
|
IRAK1 |
interleukin-1 receptor-associated kinase-1 |
P51617 |
|
|
|
|
|
IRAK4 |
interleukin-1 receptor associated kinase-4 |
Q9NWZ3 |
|
|
|
|
|
IRF3 |
interferon regulatory factor-3 |
Q14653 |
|
|
|
|
|
IRSE |
IFN-stimulated response element |
|
|
|
|
|
|
JNK1 |
c-Jun N-terminal kinase 1 |
P45983 |
MAPK8, MK08 |
|
|
|
|
MD-2 |
myeloid differentation gene-2 |
Q9Y6Y9 |
LPS co-receptor, |
|
|
|
lymphocyte antigen 96 |
|
|
|
|
MEK3 |
MAP-kinase ERK-activating kinase 3 |
P46734 |
MKK3, MAP2K3 |
|
|
|
|
MEK6 |
MAP-kinase ERK-activating kinase 6 |
P52564 |
MKK6, SAPKK3 |
|
|
|
|
MK2 |
MAP-kinase activated protein kinase-2 |
P49137 |
MAPKAP K2 |
|
|
|
|
MMS2 |
mutant sensitive to methanesulfonate-2 (in |
Q15819 |
Uev1, UB2V2 |
|
Saccharomyces cerevisiae) |
|
|
|
|
|
|
MyD88 |
myeloid differentiation primary response protein |
Q99836 |
|
|
88 |
|
|
|
|
|
|
NEDD4 |
neuronal precursor cell expressed developmentally |
P46934 |
E3 ubiquitin protein |
|
down regulated-4 |
|
ligase |
|
|
|
|
NEMO |
NFkB essential modulator |
Q9Y6K9 |
IKKg |
|
|
|
|
NFB1 |
nuclear factor kappa-B1 |
P19838 |
p105/p50 truncated |
|
|
|
|
NFB2 |
nuclear factor kappa-B2 |
Q00653 |
p100/p52 truncated |
|
|
|
|
p38 |
mitogen activation protein kinase p38a |
Q16539 |
SAPK21, MK14 |
Continued
475
Signal Transduction
Abbreviation |
Full name/description |
SwissProt |
Other names/OMIM |
|
|
entry |
|
|
|
|
|
pelle |
|
Q05652 |
|
|
|
|
|
PIAS1 |
protein inhibitor of activated STAT |
O75925 |
RNA helicase II-binding |
|
|
|
protein |
|
|
|
|
proteasome |
|
P20618 |
PSMB1, component C5 |
subunit- 1 |
|
|
|
|
|
|
|
proteasome |
|
P49721 |
PSMB2, component |
subunit- 2 |
|
|
C7-1 |
|
|
|
|
proteasome |
|
P28074 |
PSMB5, epsilon chain, |
subunit- 5 |
|
|
chain 6 |
|
|
|
|
REL-A |
reticuloendotheliosis virus like protein A |
Q04206 |
NF-k-B p65 subunit |
|
|
|
|
RING |
really interesting new gene |
|
|
|
|
|
|
S5a |
human proteasome subunit, Svedberg- |
P55036 |
Rpn10, PSMD4 |
|
sedimentation constant 5a |
|
|
|
|
|
|
SCF |
ubiquitin E-3 ligase complex comprising Skp, |
|
|
|
Cullin-1 and F-box protein |
|
|
|
|
|
|
Skp2 |
S-phase kinase-associated protein-2 |
Q13309 |
F-box/LRR-repeat |
|
|
|
protein |
|
|
|
|
SUMO-1 |
small ubiquitin-related modifier-1 |
P63165 |
RanGAP modifying |
|
|
|
protein |
|
|
|
|
TAB1 |
TAK1-binding-1 |
Q15750 |
MAP3K7IP1 |
|
|
|
|
TAB2 |
TAK1-binding-2 |
Q9NYJ8 |
MAP3K7IP2 |
|
|
|
|
TAB3 |
TAK-1-binding-3 |
Q8N5C8 |
MAP3KIP3 |
|
|
|
|
TAK1 |
transforming growth factor-B-activted kinase-1 |
O43318 |
MAP3K7 |
|
|
|
|
TANK |
TRAF-family member associated with NFkB |
Q92844 |
ITRAF |
|
activator |
|
|
|
|
|
|
TBK1 |
TANK-binding kinase 1 |
Q9UHD2 |
T2K or NAK |
|
|
|
|
TIR |
toll/interleukin-1 receptor (protein–protein |
|
|
|
interaction domain) |
|
|
|
|
|
|
TIRAP |
toll-interleukin-1-receptor (TIR) domain containing |
P58753 |
Mal |
|
adaptor protein |
|
|
|
|
|
|
TLR4 |
toll-like receptor-4 |
O00206 |
|
|
|
|
|
Continued
476
The Toll-like Receptor 4 and Signalling through Ubiquitylation
Abbreviation |
Full name/description |
SwissProt |
Other names/OMIM |
|
|
entry |
|
|
|
|
|
Toll |
refers to its remarkable effect on dorsal ventral- |
P08953 |
|
|
polarity of drosophila embryos |
|
|
|
|
|
|
TRAF3 |
TNF-receptor-associated factor-3 |
Q13114 |
|
|
|
|
|
TRAF6 |
TNF-receptor-associated factor-6 |
Q9Y4K3 |
|
|
|
|
|
TRAM |
TRIF-related adaptor molecule |
Q86XR7 |
TICAM2 Toll/IL-1R- |
|
|
|
domain containing |
|
|
|
adaptor molecule-2 |
|
|
|
|
Trcp |
Transducin-repeat containing protein |
Q9Y297 |
F-box/WD repeat |
|
|
|
protein |
|
|
|
|
TRIF |
TIR domain-containing adaptor inducing IFN |
Q8IUC6 |
TICAM1 Toll/IL-1R- |
|
|
|
domain containing |
|
|
|
adaptor molecule-1 |
|
|
|
|
Tube |
|
P22812 |
|
|
|
|
|
Ubc13 |
ubiquitin carrier-13 |
P61088 |
UBE2N (E2-conjugating |
|
|
|
enzyme) |
|
|
|
|
Ubc4 |
ubiquitin conjugating enzyme |
P62837 |
UBE2D2 (E2- |
|
|
|
conjugating enzyme) |
|
|
|
|
ubiquitin |
ubiquitously expressed |
P62988 |
|
|
|
|
|
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