The Journal of Immunology, Vol 156, Issue 2 532-538, Copyright © 1996 by American Association of Immunologists

ARTICLES

Ubiquitin-like moiety of the monoclonal nonspecific suppressor factor beta is responsible for its activity

M Nakamura, RM Xavier and Y Tanigawa
Department of Biochemistry, Shimane Medical University, Izumo, Japan.

Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressive functions. Most recently, a cDNA clone encoding MNSF beta (a subunit of MNSF) was isolated and characterized. The MNSF beta cDNA encodes 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, cDNA encoding the ubi-L region was expressed in bacteria and the recombinant product was tested for the activity. Ubi-L showed MNSF-like biologic activity without any cytotoxic action. Interestingly, the addition of ubiquitin to the assay inhibited ubi-L-induced suppression. IFN-gamma, which is known to enhance the expression of MNSF receptor, induced splenocytes to secrete ubi-L by increasing mRNA. Ubi-L has species-specific action and the ability to selectively inhibit the B cell proliferative response stimulated by soluble but not by Sepharose- bound anti-Ig Ab. In addition, okadaic acid, a serine/threonine phosphatase 1 and 2A inhibitor, showed a synergistic inhibitory action with ubi-L, indicative of the possible involvement of phosphatase(s) in the regulation of ubi-L action.

This article has been cited by other articles:

				M. Nakamura and S. Yamaguchi The Ubiquitin-like Protein MNSFbeta Regulates ERK-MAPK Cascade J. Biol. Chem., June 23, 2006; 281(25): 16861 - 16869. [Abstract] [Full Text] [PDF]

				M. Majetschak, U. Krehmeier, M. Bardenheuer, C. Denz, M. Quintel, G. Voggenreiter, and U. Obertacke Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness Blood, March 1, 2003; 101(5): 1882 - 1890. [Abstract] [Full Text] [PDF]

				H. Daino, I. Matsumura, K. Takada, J. Odajima, H. Tanaka, S. Ueda, H. Shibayama, H. Ikeda, M. Hibi, T. Machii, et al. Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells: possible involvement of STAT3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells Blood, April 15, 2000; 95(8): 2577 - 2585. [Abstract] [Full Text] [PDF]

				M. Nakamura and Y. Tanigawa Biochemical Analysis of the Receptor for Ubiquitin-like Polypeptide J. Biol. Chem., June 18, 1999; 274(25): 18026 - 18032. [Abstract] [Full Text] [PDF]

				J. R. Gruen and S. M. Weissman Evolving Views of the Major Histocompatibility Complex Blood, December 1, 1997; 90(11): 4252 - 4265. [Full Text] [PDF]