Trib1 links the MEK1/ERK pathway in myeloid leukemogenesis

Abstract

Trib1 is a myeloid oncogene that cooperates with Hoxa9 and Meis1. Although the MAPK pathway and C/EBP transcription factors are known to interact with Trib proteins, the mechanisms by which Trib1 contributes to myeloid leukemogenesis remains to be clarified. Here we report that interaction between Trib1 and MEK1 is required for Trib1-induced leukemogenesis. The C-terminal ILLHPWF motif that is well conserved among Trib family proteins is required for MEK1 binding, enhancement of ERK phosphorylation, enhanced self-renewal activity of bone marrow cells and leukemogenic activity by Trib1. The motif is also important for Trib1-induced C/EBPα degradation though interaction between Trib1 and C/EBPα is not necessary. Inhibition of ERK phosphorylation suppressed Trib1-induced C/EBPα degradation, indicating an important role for Trib1/MEK1 interaction. These results suggest that Trib1 may be a key mediator between the RTK-MAPK pathway and the C/EBP transcription factor in myeloid leukemogenesis.