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Biochemistry. 1996 Jun 25;35(25):8216-25.

Human pro-tumor necrosis factor is a homotrimer.

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  • 1Department of Tumor Biology, University of Texas, M. D. Anderson Cancer Center, Houston, 77030, USA.

Abstract

The structure of human transmembrane pro-TNF-alpha was studied both in intact cell systems and in an in vitro translation system. In intact cell systems (LPS-induced THP-1 and TNF cDNA-transfected COS-7), a trimer of pro-TNF was detected after chemical cross-linking based on its molecular weight in Western blotting analysis. The trimer was shown to be a TNF-specific protein and could be partially cleaved to 26-kDa pro-TNF monomers by cleaving the cross-linkers. The trimeric structure was assembled intracellularly, because it could be detected in both the in vitro microsomal translation system and in THP-1 cells coincident with the appearance of pro-TNF in the cell lysate, prior to secretion of mature TNF. To further analyze the relationship between the trimeric structure and the biological activity of pro-TNF, we characterized several noncleavable pro-TNF deletion mutants. We observed a correlation between expression of TNF cytotoxicity in a juxtacrine fashion and detection of trimer. Thus, human pro-TNF-alpha, like the secreted mature TNF-alpha, has trimeric structure which is assembled intracellularly before transport to the cell surface and is apparently required for mediating its biologic activity.

PMID:
8679576
[PubMed - indexed for MEDLINE]
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