1 an adapter TNF receptor-associated factor 4 (
TRAF4).
2 F5, and TRAF6, but not with TRAF2, TRAF3, or
TRAF4.
3 which is associated with Rac1 activation by
TRAF4.
4 f p47(phox) and the conserved TRAF domain of
TRAF4.
5 sociate and binds to human TRAF1, TRAF2, and
TRAF4.
6 Furthermore, overexpression of
TRAF4 abrogated the ability of dimerization to prevent t
7 An active mutant of
TRAF4 activated the NADPH oxidase downstream of the Rho
8 KK4 binds the TRAF domain of TRAF4 and MEKK4/
TRAF4 activation of JNK is inhibited by expression of th
9 TRAF4 also inhibited the NF-kappaB response, whereas TRA
10 er basic signaling cassettes at the level of
TRAF4 and an NAD(P)H oxidase.
11 and Axin each bind and activate MEKK4, with
TRAF4 and Axin binding to the kinase domain and GADD45 b
12 we show that similar to the interaction with
TRAF4 and Axin, the kinase domain of MEKK4 interacts wit
13 es in NOD2 are required for interaction with
TRAF4 and inhibition of NOD2 signaling because mutation
14 tructural basis for the atypical function of
TRAF4 and its atypical role in NOD2 signaling.
15 Here, we show that endogenous
TRAF4 and MEKK4 associate in both human K562 cells and m
16 urther demonstrated by the colocalization of
TRAF4 and MEKK4 in cells.
17 activate JNK independently, coexpression of
TRAF4 and MEKK4 results in synergistic activation of JNK
18 MEKK4 binds the TRAF domain of
TRAF4 and MEKK4/TRAF4 activation of JNK is inhibited by
19 TRAF4 and misshapen (MSN) act downstream of Draper to ac
20 sisting of Smurf1-mediated ubiquitination of
TRAF4 and Rac1 activation.
21 Mechanistically, we found that
TRAF4 and TRAF6 used the same TRAF binding sites on Act1
22 The interaction of MEKK4 and
TRAF4 are further demonstrated by the colocalization of
23 pression, breast cancer cells overexpressing
TRAF4 are more resistant to stress-induced death.
24 We have identified
TRAF4 as a p53-regulated gene in a microarray screen usi
25 Our results uncover new functions for
TRAF4 as a Smurf1-regulated mediator of BMP and Nodal si
26 llowed by bioinformatic screening identified
TRAF4 as a substrate for IKKalpha.
27 s factor (TNF)-receptor-associated factor-4 (
TRAF4)
as a new target of Smurf1, which polyubiquitylate
28 e identify TNF receptor associated factor 4 (
TRAF4)
as a novel Draper binding partner that is require
29 ctor-associated factor (TRAF) family member,
TRAF4,
as a key negative regulator of NOD2 signaling.
30 ecrosis factor receptor-associated factor 4 (
TRAF4)
at K190.
31 However, unlike
TRAF4,
Axin, and GADD45, GSK3beta inhibits MEKK4 activit
32 se mutation of these residues abrogated both
TRAF4 binding and inhibition of NOD2.
33 Additionally, it defines a
TRAF4 binding motif within NOD2 involved in termination
34 xpression of the p47(phox) binding domain of
TRAF4 blocked endothelial cell JNK activation by TNFalph
35 mechanism, we showed that the TRAF domain of
TRAF4 bound to the N-terminal TRAF-like region of the de
36 levels, indicating endogenous regulation of
TRAF4 by Smurf1.
37 addition, a fusion between p47(phox) and the
TRAF4 C terminus constitutively activated JNK, and this
38 defined CD40-responsive genes cIAP2, TRAF1,
TRAF4/
CART and DR3 were unaffected.
39 found that IL-25 responses were impaired in
Traf4 (-/-)
cells.
40 TRAF4-
deficient mice are born with a constricted upper t
41 Primary cells from
TRAF4-
deficient mice displayed markedly enhanced IL-17-a
42 To address this issue, we have generated
TRAF4-
deficient mice.
43 MOG35-55 specific wild-type Th17 cells into
TRAF4-
deficient recipient mice induced an earlier onset
44 TRAF4 directly associated with the focal contact scaffol
45 TRAF4 expression is positively correlated with SRC-3 exp
46 ing embryo, as well as in the adult, lack of
TRAF4 expression results in a localized, developmental d
47 TRAF4,
GADD45, and Axin each bind and activate MEKK4, wi
48 Importantly, although
TRAF4 has little or no ability to activate JNK independe
49 In contrast to its other family members,
TRAF4 has not been shown to bind to a member of the tumo
50 TRAF4 has previously been shown to activate JNK through
51 of a normal immune system, the importance of
TRAF4 has remained unclear.
52 Knockdown of embryonic
TRAF4 impairs signaling, neural crest development and ne
53 Therefore the role of
TRAF4 in a signaling pathway has not yet been establishe
54 udy reveal the necessity of a unique role of
TRAF4 in restricting the effects of IL-17 signaling and
55 Despite widespread expression of
TRAF4 in the developing embryo, as well as in the adult,
56 Coexpression of p47(phox) and
TRAF4 increased oxidant production and JNK activation, w
57 Interestingly, the overexpression of
TRAF4 induces apoptosis and suppresses colony formation.
58 TRAF4 inhibits NOD2-induced NF-kappaB activation and dir
59 Active
TRAF4 initiated robust membrane ruffling through Rac1, P
60 Furthermore,
TRAF4 interacted with dimeric p75(NTR), whereas TRAF2 in
61 dary screen of endothelial cell proteins for
TRAF4-
interacting partners yielded a number of proteins
62 TRAF4 interacts with the kinase domain of MEKK4.
63 TRAF4 is a member the TRAF family of adaptor proteins th
64 Like IKKalpha,
TRAF4 is atypical within its family because it is the on
65 We further show that
TRAF4 is essential for the migration of both normal mamm
66 TRAF4 is one of six identified members of the family of
67 These data demonstrate that
TRAF4 is required to regulate the anastomosis of the upp
68 TRAF4 is specifically regulated by p53 in response to te
69 interfering RNA knockdown of Smurf1 elevates
TRAF4 levels, indicating endogenous regulation of TRAF4
70 In addition,
TRAF4,
like p47(phox), was recovered largely in the cyto
71 TRAF4 localizes to the cytoplasm and appears to remain i
72 correlation that the orphan adaptor protein
TRAF4 may play a role in p53-mediated proapoptotic signa
73 This
TRAF4-
mediated inhibition of HAUSP then led to the loss
74 underlying molecular mechanism for SRC-3 and
TRAF4-
mediated resistance to cytotoxic agents.
75 Administering IL-25 to
Traf4 (-/-)
mice resulted in blunted airway eosinophilia
76 In the frog Xenopus laevis,
TRAF4 mRNA is stored maternally in the egg animal pole,
77 TRAF1, TRAF2, TRAF3, and TRAF6, but not
TRAF4 or TRAF5, bound directly to the CD40 cytoplasmic d
78 rest development and neural folding, whereas
TRAF4 overexpression boosts signaling and expands the ne
79 ast cancers and further found that SRC-3 and
TRAF4 overexpression diminished cytotoxic stress-induced
80 h this cellular function, we also found that
TRAF4 overexpression in breast cancer patients was assoc
81 TRAF2-p75(NTR),
TRAF4-
p75(NTR), and TRAF6-p75(NTR) interactions modulate
82 usceptibility protein, NOD2, is required for
TRAF4 phosphorylation and subsequent inhibition of NOD2
83 leukin, or Toll-like receptors, we find that
TRAF4 potentiates BMP and Nodal signaling.
84 The murine
TRAF4 promoter contains a functional p53 DNA-binding sit
85 Mechanistically,
TRAF4 recruited the E3-ligase SMURF2, to degrade the IL-
86 identify MEKK4 as the MAPK kinase kinase for
TRAF4 regulation of the JNK pathway.
87 This study indicates that
TRAF4-
SMURF2-mediated DAZAP2 degradation is a crucial in
88 Our data suggest that
TRAF4 specifies a molecular address within focal complex
89 Furthermore,
TRAF4 stimulates MEKK4 kinase activity by promoting MEKK
90 resides within an exaggerated beta-bulge in
TRAF4 that is not present in the other TRAF proteins, an
91 The ability of
TRAF4 to promote cell migration is also dependent on Smu
92 ation is required for proper localization of
TRAF4 to tight junctions in confluent epithelial cells.
93 ew target of Smurf1, which polyubiquitylates
TRAF4 to trigger its proteasomal destruction.
94 d TRAF family proteins (TRAF1, TRAF2, TRAF3,
TRAF4,
TRAF5, and TRAF6), whereas the TD of SPOP interac
95 to TRAF2 and TRAF3, direct binding of TRAF1,
TRAF4,
TRAF5, or TRAF6 to CD40 was not detected.
96 roach, we identified a SRC-3 downstream gene-
TRAF4 (
tumor necrosis factor [TNF] receptor associated-f
97 Notably, IL-25R recruitment of
TRAF4 was required for the ACT1/IL-25R interaction.
98 IKKalpha's phosphorylation of serine-426 on
TRAF4 was required for this negative regulation.
99 ssion of proapoptotic proteins caspase-9 and
TRAF4 was seen in endothelial cells and smooth muscle ce
100 Using the K190R mutant of
TRAF4,
we demonstrate that Smurf1-induced ubiquitination
101 NF receptor-associated factor-2 (TRAF2), and
TRAF4 were clearly inducible via CD40 in B cells but not
102 se adaptor p47(phox) and its binding partner
TRAF4 were sequestered within nascent, focal complexlike
103 as the proapoptotic molecules caspase-3 and
TRAF4,
which are downregulated during development, and t
104 g sites on Act1, allowing the competition of
TRAF4 with TRAF6 for the interaction with Act1.