HUBC9 ASSOCIATES WITH MEKK1 AND TYPE-I TNF-ALPHA RECEPTOR AND STIMULATES NF-KAPPA-B ACTIVITY

hUBC9, an E2 ubiquitin conjugating enzyme, was identified by yeast two -hybrid screening and coprecipitation studies to interact with MEKK1 a nd the type I TNF-alpha receptor, respectively. Because both of these proteins regulate NF kappa B activity, the role of hUBC9 in modulating NF kappa B activity was investigated. Overexpression of hUBC9 in HeLa cells stimulated the activity of NF kappa B as determined by NF kappa B reporter and IL-6 secretion assays, hUBC9 also synergized with MEKK 1 to activate NF kappa B reporter activity. Thus, hUBC9 modulates NF k appa B activity which, at least in part, can be attributed to its inte raction with MEKK1 and the type I TNF-alpha receptor. (C) 1998 Federat ion of European Biochemical Societies.