TRAF4

TRAF4

A gene on chromosome 17q11-q21.3 that encodes TNF receptor-associated factor 4, an adapter protein and signal transducer which links members of the tumour necrosis factor receptor (TNFR) family to various signalling pathways. TRAF4 plays a role in JNK activation, in NF-kappaB activation in response to Toll-like receptor signalling, and in regulating cell survival and apoptosis. It is required for normal skeletal and normal respiratory tract development, is required for RPS6KB1 activation in response to TNF signalling, and modulates TRAF6 activities.
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IL-17A stimulation can recruit TRAF4 to the IL-17 receptor complex, and TRAF4 can be a negative modulator of IL-17-mediated signaling by competing with TRAF6 for Act1 binding [20].
(59-61) However, these deubiquitinating factors are not the only negative regulators of NODs; the latter include TRAF4 that binds directly to NOD2.
(2011) A novel motif in the Crohn's disease susceptibility protein, NOD2, allows TRAF4 to down-regulate innate immune responses.
(2012) IkappaB kinase alpha phosphorylation of TRAF4 downregulates innate immune signaling.
The mutants which display only spina bifida are the FGFR1[alpha] chimeric mutant [94], Traf4 mutant [95], the Shp2 chimeric mutant [96], the axial defects mutant [97], glial cell missing-1 [98], and vacuolated lens [99].
Chenard et al., "Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development," Mechanisms of Development, vol.
Shah, "Acute tumor necrosis factor alpha signaling via NADPH oxidase in microvascular endothelial cells: role of [p47.sup.phox] phosphorylation and binding to TRAF4," Molecular and Cellular Biology, vol.
Based on bioinformatic studies, a main target gene for miR-4284 is tumor necrosis factor receptor-associated factor 4 (TRAF4), which is recruited to the active TGF-[beta] receptor complex 4 (TRAF4) as a key component mediating pro-oncogenic TGF-[beta]-induced SMAD and non-SMAD signaling.
TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis.
Table 1: The target gene predicted for miR-4284 and miR-4484 as well as their role in cells Target genes Roles in cells miR-4284 TRAF4, BCL 10, Apoptosis, HDAC, HOXA1, differentiation, PTEN proliferation miR-4484 AATF, PTPN14, PI3K, PTEN Apoptosis
Unlike TRAF6, the molecular mechanism of TRAF4 in multiple signaling pathways triggered by TNFR-related proteins remains enigmatic.
Recent studies in immune cells and transgenic mice regarding the role of TRAF4 and TRAF6 have revealed that they share the same binding sites, yet comprehensive study of TRAF4 and TRAF6 in IBD is still lacking [11].