Oeda E, Oka Y, Miyazono K, Kawabata M
Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research and Research for the Future Program, Japan Society for the Promotion of Science, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
J Biol Chem. 1998 Apr 17;273(16):9353-6. doi: 10.1074/jbc.273.16.9353.
Decapentaplegic (Dpp) is a Drosophila member of bone morphogenetic proteins, which belong to the transforming growth factor-beta superfamily. Members of this family regulate a variety of biological processes such as cell proliferation, morphogenesis, immune response, and apoptosis. Dpp plays a critical role in many aspects of Drosophila development. Members of the transforming growth factor-beta superfamily bind to two different types of serine/threonine kinase receptors, termed type I and type II. Type I receptors act as downstream components of type II receptors in the receptor complexes. Therefore, intracellular proteins that interact with the type I receptors are likely to play important roles in signaling. Several proteins have been identified through protein-protein interaction screenings. We identified Drosophila inhibitor of apoptosis (DIAP) 1 as an interacting protein of a Dpp type I receptor, Thick veins (Tkv). DIAP1 associates with Tkv in vivo. The binding region in DIAP1 is mapped to its C-terminal RING finger region. DIAP2, another Drosophila member of the inhibitor of apoptosis protein family, also interacts with Tkv in vivo. These data suggest that DIAP1 and DIAP2 may be involved, possibly as negative regulators, in the Dpp signaling pathway, which leads to cell apoptosis.
Decapentaplegic(Dpp)是骨形态发生蛋白的果蝇成员,骨形态发生蛋白属于转化生长因子-β超家族。该家族成员调节多种生物学过程,如细胞增殖、形态发生、免疫反应和细胞凋亡。Dpp在果蝇发育的许多方面起着关键作用。转化生长因子-β超家族成员与两种不同类型的丝氨酸/苏氨酸激酶受体结合,即I型和II型。I型受体在受体复合物中作为II型受体的下游成分发挥作用。因此,与I型受体相互作用的细胞内蛋白可能在信号传导中发挥重要作用。通过蛋白质-蛋白质相互作用筛选已鉴定出几种蛋白质。我们鉴定出果蝇凋亡抑制蛋白(DIAP)1作为Dpp I型受体Thick veins(Tkv)的相互作用蛋白。DIAP1在体内与Tkv相关联。DIAP1中的结合区域定位于其C末端的RING指状区域。DIAP2是凋亡抑制蛋白家族的另一个果蝇成员,在体内也与Tkv相互作用。这些数据表明,DIAP1和DIAP2可能作为负调节因子参与导致细胞凋亡的Dpp信号通路。