Functional mapping and identification of novel regulators for the Toll/Interleukin-1 signalling network by transcription expression cloning

Identification of Tribbles-1 as a Novel Binding Partner of Foxp3 in Regulatory T Cells

“…This interaction was no longer significant when TRIB1 was deleted of its N terminus domain. Such a nuclear interaction fits well with the fact that the N terminus domain of TRIB1 is particularly important for transporting TRIB1 to the nucleus (3,43) and the fact that Foxp3 is principally expressed in the nucleus (17). This interaction was confirmed by fluorescent microscopy subsequent to the PCA, which again clearly showed the interaction between TRIB1 and Foxp3 in the nucleus.…”

Tribbles: novel regulators of cell function; evolutionary aspects

“…When trb is overexpressed in the posterior compartment of the wing imaginal disk, the wing is made up of fewer but larger cells, compared with controls. (This enlarged phenotype was also seen in HeLa cells, when human trb-3 was overexpressed [9].) Flow cytometry analysis suggested that trb expressing cells were mainly in G2/M phase.…”

“…However, the biological relevance of this interaction is still unknown as there has been no independent confirmation and further characterisation of trb-1/12-LOX binding. Our group have reported recently the identification of human tribbles-1 as a novel regulator of AP-1 activation in a screen [9], which is designed to rapidly annotate signalling network components based on their function [13][14][15]. Further characterisation of trb-1 function revealed that this protein (similarly to trb-3) binds to the 'middle layer' of kinases in the MAPK network, the MAPKKs [16].…”

Trib1 links the MEK1/ERK pathway in myeloid leukemogenesis

“…The IL(L/D)HPW(F/L) motif is well conserved in 3 mammalian Trib proteins. 15 Moreover, the conservation is extended to invertebrates and the tryptophan residue is invariably conserved even in drosophila tribbles. 16 We found that the motif is required for MEK1 binding, and the mutant that lacks the entire motif as well as the tryptophan mutant lost the binding activity.…”

“…10 Trib family proteins retain high sequence homologies to one another and each possesses a highly conserved, single kinase-like domain in the middle of the proteins. 15 Short conserved motifs are also scattered both in N-and C-terminal regions. 16 To examine the domains responsible for MEK1 binding as well as enhanced self-renewal activity of bone marrow cells, we generated a series of Trib1 deletion mutants ( Figure 3A).…”