包括 PGRMC1 在内的蛋白复合物和与肌动蛋白相关的蛋白被 AG-205 破坏。

Protein complexes including PGRMC1 and actin-associated proteins are disrupted by AG-205.

机构信息

School of Biomedical Sciences, Charles Sturt University, Wagga, Wagga, NSW, 2650, Australia.

Department of Gynecology and Obstetrics, University Women's Hospital of Düsseldorf, Düsseldorf, Germany.

出版信息

Biochem Biophys Res Commun. 2020 Mar 26;524(1):64-69. doi: 10.1016/j.bbrc.2019.12.108. Epub 2020 Jan 21.

DOI:10.1016/j.bbrc.2019.12.108

PMID:31980178

Abstract

PGRMC1 is a protein from the MAPR family with a range of cellular functions. PGRMC1 has been described to play a role in fertility, neuroprotection, steroidogenesis, membrane trafficking and in cancer cell biology. PGRMC1 represents a likely key regulator of cell metabolism and proliferation, as well as a potential target for anti-cancer therapies. To further understand the functions of PGRMC1 and the mechanism of the small molecule inhibitor of PGRMC1, AG-205, proteins differentially bound to PGRMC1 were identified following AG-205 treatment of MIA PaCa-2 cells. Our results suggest that AG-205 influences PGRMC1 interactions with the actin cytoskeleton. The binding of two PGRMC1-associated proteins that support this, RACK1 and alpha-Actinin-1, was reduced following AG-205 treatment. The biology associated with PGRMC1 binding partners identified here merits further investigation.

摘要

PGRMC1 是 MAPR 家族的一种蛋白，具有多种细胞功能。PGRMC1 被描述为在生育、神经保护、类固醇生成、膜运输以及癌细胞生物学中发挥作用。PGRMC1 代表细胞代谢和增殖的一个重要调节因子，也是抗癌疗法的一个潜在靶点。为了进一步了解 PGRMC1 的功能和 PGRMC1 小分子抑制剂 AG-205 的作用机制，我们在 MIA PaCa-2 细胞中用 AG-205 处理后，鉴定了与 PGRMC1 差异结合的蛋白质。我们的结果表明，AG-205 影响 PGRMC1 与肌动蛋白细胞骨架的相互作用。AG-205 处理后，与支持这一作用的两种 PGRMC1 相关蛋白 RACK1 和α-辅肌动蛋白-1 的结合减少。与这里鉴定的 PGRMC1 结合伙伴相关的生物学值得进一步研究。