Abstract：
Striatin and SG2NA are scaffold proteins that form signaling complexes called STRIPAK. It has been associated with developmental abnormalities, cancer, and several other diseases. Our earlier studies have shown that SG2NA forms a complex with the cancer-associated protein DJ-1 and the signaling kinase Akt, promoting cancer cell survival. In the present study, we used bioinformatics analyses to confirm the existence of two isoforms of human SG2NA, i.e., 78 and 87 kDas. In addition, several smaller isoforms like 35 kDa were also seen in western blot analyses of human cell lysates. The expression of these isoforms varies between different cancer cell lines of human origin. Also, the protein levels do not corroborate with its transcript levels, suggesting a complex regulation of its expression. In breast tumor tissues, the expression of the 35 and 78 kDa isoforms was higher as compared to the adjacent normal tissues, while the 87 kDa isoform was found in the breast tumor tissues only. With the progression of stages of breast cancer, while the expression of 78 kDa isoform decreased, 87 kDa became undetectable. In co-immunoprecipitation assays, the profile of the SG2NA interactome in breast tumors vis-à-vis adjacent normal breast tissues showed hundreds of common proteins. Also, some proteins were interacted with SG2NA in breast tumor tissues only. We conclude that SG2NA is involved in diverse cellular pathways and has roles in cellular reprogramming during tumorigenesis of the breast.
摘要：
纹状体蛋白和SG2NA是形成称为STRIPAK的信号复合物的支架蛋白。它与发育异常有关，癌症,和其他几种疾病。我们早期的研究表明，SG2NA与癌症相关蛋白DJ-1和信号激酶Akt形成复合物，促进癌细胞存活。在本研究中,我们使用生物信息学分析来确认人类SG2NA的两种亚型的存在，即，78和87kDas。此外,在人细胞裂解物的蛋白质印迹分析中也观察到几种较小的同种型,如35kDa。这些同种型的表达在人来源的不同癌细胞系之间变化。此外，蛋白质水平与转录水平没有确证，表明其表达的复杂调节。在乳腺肿瘤组织中，与邻近的正常组织相比，35和78kDa亚型的表达更高，而87kDa亚型仅在乳腺肿瘤组织中发现。随着乳腺癌分期的进展，而78kDa亚型的表达减少，87kDa变得不可检测。在免疫共沉淀试验中,与邻近的正常乳腺组织相比，乳腺肿瘤中SG2NA相互作用组的图谱显示出数百种常见蛋白。此外，一些蛋白仅在乳腺肿瘤组织中与SG2NA相互作用。我们得出结论，SG2NA参与多种细胞途径，并在乳腺肿瘤发生过程中在细胞重编程中发挥作用。
