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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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