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XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1–TAK1 in the BMP signaling pathway
Author(s) -
Yamaguchi Kyoko,
Nagai Shinichi,
NinomiyaTsuji Jun,
Nishita Michiru,
Tamai Katsuyuki,
Irie Kenji,
Ueno Naoto,
Nishida Eisuke,
Shibuya Hiroshi,
Matsumoto Kunihiro
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.1.179
Subject(s) - xiap , biology , inhibitor of apoptosis , signal transduction , microbiology and biotechnology , receptor , apoptosis , inhibitor of apoptosis domain , cancer research , genetics , caspase , programmed cell death
Signals elicited by transforming growth factor‐β (TGF‐β) superfamily ligands are generated following the formation of heteromeric receptor complexes consisting 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 morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos. However, the events leading from receptor activation to TAK1 activation remain to be identified. A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1–TAK1. The human X‐chromosome‐linked inhibitor 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 ventralization of Xenopus embryos in a TAB1–TAK1‐dependent manner. Furthermore, a truncated 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 receptors and TAB1–TAK1.