Mitogene-inducible gene-6 (Mig-6), an adaptor molecule containing the Cdc42/Rac interaction and binding (CRIB) domain, is rapidly induced by mitogenic and stressful stimuli, and sustained mig-6 expression is observed in chronic pathological conditions. The function of this molecule has remained elusive. We find that mig-6 is constitutively expressed in many human cancer cell lines, and Mig-6 is cleaved into the NH2-terminal region containing the CRIB domain and the remainder of the COOH-terminal region by limited proteolytic processing. We report here that full-length Mig-6, but not CRIB domain-deleted Mig-6 (ΔMig-6) or uncleavable mutant of Mig-6 (Mig-6-S38A), induces transcriptional activation of nuclear factor of κB (NFκB), which is inhibited by inhibitor of κBα (IκBα), and that the processed NH2-terminal region of Mig-6 but not the full length is bound with IκBα through its NFκB binding region. These findings suggest that the processed CRIB domain of Mig-6 will compete with NFκB for IκBα and result in NFκB activation. This novel NFκB activation pathway provides new insights regarding tumorigenesis, and the specific inhibition of the cleavage of Mig-6 may be a target for clinical treatment.
|Number of pages||4|
|Publication status||Published - Oct 15 2002|
All Science Journal Classification (ASJC) codes
- Cancer Research