XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway

Signals elicited by transforming growth factor-p (TGF-P) superfamily ligand s are generated following the formation of heteromeric receptor complexes c onsisting of type I and type II receptors, TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone mor phogenetic protein (BMP) signaling pathway involved in mesoderm induction a nd patterning in early Xenopus embryos. However, the events leading from re ceptor activation to TAK1 activation remain to be identified. A yeast inter action screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1, The human X-chromosome-linked inhibito r of apoptosis protein (XIAP) was isolated as a TAB1-binding protein. XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventrali zation of Xenopus embryos in a TAB1-TAK1-dependent manner. Furthermore, a t runcated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively active BMP type I receptor. These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptor s and TAB1-TAK1.