APOBEC3酶家族的蛋白相互作用地图揭示了在细胞功能中的除菌独立作用
Gwendolyn M Jang1, Arun Kumar Annan Sudarsan2, Arzhang Shayeganmehr2
1Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, California, USA; J. David Gladstone Institutes, Gladstone Institute for Data Science and Biotechnology, San Francisco, California, USA.
Molecular & cellular proteomics : MCP
|March 28, 2024
概括
人类APOBEC3酶对先天免疫至关重要,与RNA和蛋白质相互作用. 错误调节将APOBEC3与癌症联系起来,在RNA生物学和瘤抑制方面发现了新的相互作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 人类APOBEC3酶是对病毒的内在免疫力至关重要的cytidine deaminases.
- 它们的功能是通过去胺化细胞因子,禁活病毒基因组,并具有去胺独立的抗病毒活性.
- 错误调节的APOBEC3表达会导致基因组不稳定,并导致癌症的发展.
研究的目的:
- 阐明人类APOBEC3酶的蛋白相互作用网络.
- 了解RNA在APOBEC3相互作用和功能中的作用.
- 研究APOBEC3相互作用与癌症生物学之间的潜在联系.
主要方法:
- 使用亲和净化质谱法 (AP-MS) 来确定蛋白质相互作用.
- 蛋白质-蛋白质和蛋白质-RNA介导的相互作用被绘制为APOBEC3家族成员.
- 功能性试验评估了APOBEC3B与prefoldin 5 (PFD5) 相互作用对c-Myc降解的影响.
主要成果:
- 在APOBEC3C,APOBEC3G和APOBEC3H与结合体蛋白以及tRNA甲基化/ncRNA输出因子之间发现了新的RNA介导相互作用.
- 在APOBEC3B,APOBEC3D,APOBEC3F和prefoldin家族之间发现了RNA独立的相互作用.
- APOBEC3B与PFD5的相互作用抑制了PFD5降低瘤基因c-Myc.c的能力.
结论:
- APOBEC3酶参与各种RNA介导和RNA独立的相互作用,揭示了RNA生物学中的新角色.
- 非冗余蛋白质-蛋白质相互作用,包括与瘤抑制剂的相互作用,表明APOBEC3s在癌症生物学中起着重要作用.
- 鉴定到的相互作用为了解APOBEC3功能及其对疾病的影响提供了新的途径.
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