Background Membrane-associated progesterone receptors are restricted to the endoplasmic reticulum and are shown to regulate the activity of cytochrome P450 enzymes which are involved in steroidogenesis or drug detoxification. PGRMC1 and PGRMC2 belong to the membrane-associated progesterone receptor family and are of interest due to their suspected role during cell cycle. PGRMC1 and PGRMC2 are thought to bind to each other; thereby suppressing entry into mitosis. We could previously report that PGRMC2 interacts with the nucleoporin ALADIN which when mutated results in the autosomal recessive disorder triple A syndrome. ALADIN is a novel regulator of mitotic controller Aurora kinase A and depletion of this nucleoporin leads to microtubule instability. Results In the current study, we present that proliferation is decreased when ALADIN, PGRMC1 or PGRMC2 are over-expressed. Furthermore, we find that depletion of ALADIN results in mislocalization of Aurora kinase A and PGRMC1 in metaphase cells. Additionally, PGRMC2 is over-expressed in triple A patient fibroblasts. Conclusion Our results emphasize the possibility that loss of the regulatory association between ALADIN and PGRMC2 gives rise to a depletion of PGRMC1 at kinetochore fibers. This observation may explain part of the symptoms seen in triple A syndrome patients.

中文翻译：

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患有有丝分裂缺陷的 Triple A 患者细胞无法将 PGRMC1 定位到有丝分裂动粒纤维。

背景 膜相关孕酮受体仅限于内质网，并显示出调节参与类固醇生成或药物解毒的细胞色素 P450 酶的活性。PGRMC1 和 PGRMC2 属于膜相关的孕酮受体家族，并且由于它们在细胞周期中的可疑作用而受到关注。PGRMC1 和 PGRMC2 被认为相互结合；从而抑制进入有丝分裂。我们之前可以报道 PGRMC2 与核孔蛋白 ALADIN 相互作用，当其突变时会导致常染色体隐性遗传病三 A 综合征。ALADIN 是有丝分裂控制器 Aurora 激酶 A 的新型调节剂，这种核孔蛋白的消耗会导致微管不稳定。结果在目前的研究中，我们提出当 ALADIN、PGRMC1 或 PGRMC2 过表达。此外，我们发现 ALADIN 的消耗导致 Aurora 激酶 A 和 PGRMC1 在中期细胞中的错误定位。此外，PGRMC2 在三 A 患者成纤维细胞中过度表达。结论 我们的结果强调了 ALADIN 和 PGRMC2 之间调节关联的丧失可能导致着丝粒纤维中 PGRMC1 的消耗。这一观察结果可以解释 AAA 综合征患者的部分症状。结论 我们的结果强调了 ALADIN 和 PGRMC2 之间调节关联的丧失可能导致着丝粒纤维中 PGRMC1 的消耗。这一观察结果可以解释 AAA 综合征患者的部分症状。结论 我们的结果强调了 ALADIN 和 PGRMC2 之间调节关联的丧失可能导致着丝粒纤维中 PGRMC1 的消耗。这一观察结果可以解释 AAA 综合征患者的部分症状。