UBIQUITIN-LIKE MOIETY OF THE MONOCLONAL NONSPECIFIC SUPPRESSOR FACTOR-BETA IS RESPONSIBLE FOR ITS ACTIVITY

Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific sup pressive functions, Most recently, a cDNA clone encoding MNSF beta (a subunit of MNSF) was isolated and characterized, The MNSF beta cDNA en codes a 14,5-kDa fusion protein with MNSF-like activity consisting of an 8-kDa ubiquitin-like segment (ubi-L) and the ribosomal protein S30 (6.5 kDa). To determine whether ubi-L itself has biologic activity, cD NA encoding the ubi-L region was expressed in bacteria and the recombi nant product was tested for the activity, Ubi-L showed MNSF-like biolo gic activity without any cytotoxic action, Interestingly, the addition of ubiquitin to the assay inhibited ubi-L-induced suppression, IFN-ga mma, which is known to enhance the expression of MNSF receptor, induce d splenocytes to secrete ubi-L by increasing mRNA, Ubi-L has species-s pecific action and the ability to selectively inhibit the B cell proli ferative response stimulated by soluble but not by Sepharose-bound ant i-Ig Ab, In addition, okadaic acid, a serine/threonine phosphatase 1 a nd 2A inhibitor, showed a synergistic inhibitory action with ubi-L, in dicative of the possible involvement of phosphatase(s) in the regulati on of ubi-L action.