SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins

SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins
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DOI:
10.1016/s0898-6568(00)00129-7
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发表时间:
2000-12-01
影响因子:
4.8
通讯作者:
Bogler, O
Bogler, O
中科院分区:
生物学2区
文献类型:
--
作者:
Borinstein, SC;Hyatt, MA;Bogler, O

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src同源性3(SH 3)编码的在致瘤性星形胶质细胞(SETA)基因中表达的表达与培养物中的星形胶质细胞转化和成人脑中的肿瘤相关。SETA与凋亡调节因子凋亡相关基因2(ALG-2)相互作用蛋白1(AIP I)结合,并调节星形胶质细胞的凋亡。SETA的蛋白质结构预测揭示了两个SH 3结构域,而相关蛋白质据报道有三个。在这里,我们报告了一个额外的SH 3结构域N-末端的识别到以前确定的SETA序列。酵母双杂交筛选p53(-/-)星形胶质细胞cDNA文库与此; SH 3结构域确定了一个新的基因,SETA结合蛋白I(SB 1),与肾肿瘤抗原,NY-REN-45的55%的氨基酸同一性。体外对抗和免疫共沉淀实验证实了SB 1与SETA的结合。SETA与CD 2蛋白、原癌基因c-Cbl和信号转导分子Grb 2结合,并可通过其C-末端卷曲螺旋(CC)结构域二聚化的证据也被提出。(C)2000 Elsevier Science Inc. All rights reserved.
Expression of the src homology 3 (SH3)-encoding, expressed in tumorigenic astrocytes (SETA) gene is associated with astrocyte transformation in culture and tumors in the adult brain. SETA binds to the apoptosis regulator apoptosis-linked gene 2 (ALG-2) interacting protein 1 (AIP I), and modulates apoptosis in astrocytes. The predicted protein structure of SETA revealed two SH3 domains, while related proteins were reported to have three. Here we report the identification of an additional SH3 domain N-terminal to the previously identified SETA sequence. Yeast two-hybrid screening of a p53(-/-) astrocyte cDNA library with this; SH3 domain identified a novel gene, SETA binding protein I (SB1), with 55% amino acid identity to the renal tumor antigen, NY-REN-45. In vitro confrontation and coimmunoprecipitation experiments confirmed the binding of SB1 to SETA. Evidence that SETA binds to the CD2 protein, the proto-oncogene c-Cbl, and the signal transduction molecule Grb2, and can dimerize via its C-terminal coiled coil (CC) domain is also presented. (C) 2000 Elsevier Science Inc. All rights reserved.