Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2),and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2 beta

Metalloprotease-disintegrins are a family of transmembrane glycoproteins th at have a role in fertilization, sperm migration, myoblast fusion, neural d evelopment and ectodomain shedding. In the present study we used the yeast two-hybrid system to search for proteins that interact with the cytoplasmic domain of two metalloproteas-disintegrins, tumour necrosis factor alpha co nvertase (TACE; ADAM17) and MDC9 (ADAM9; meltrin gamma). We have identified mitotic arrest deficient 2 (MAD2) as a binding partner of the TACE cytopla smic domain, and a novel MAD2-related protein, MAD2 beta, as a binding part ner of the MDC9 cytoplasmic domain. MAD2 beta has 23% sequence identity wit h MAD2, which is a component of the spindle assembly (or mitotic) checkpoin t mechanism. Northern blot analysis of human tissues indicates that MAD2 be ta mRNA is expressed ubiquitously. The interaction of the TACE and MDC9 cyt oplasmic domains with their binding partners has been confirmed biochemical ly. The independent identification of MAD2 and MAD2 beta as potential inter acting partners of distinct metalloprotease-disintegrins raises the possibi lity of a link between metalloprotease-disintegrins and the cell cycle, or of functions for MAD2 and MAD2 beta that are not related to cell cycle cont rol.