State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
Chem Biodivers. 2020 Dec;17(12):e2000743. doi: 10.1002/cbdv.202000743. Epub 2020 Nov 26.
Both Raptor and Rictor are the key components in the complexes of mammalian target of rapamycin (mTOR), which play a vital role in mediating autophagy. Unlike mTOR, the regulatory role of either Raptor or Rictor in the regulation of autophagic process is relatively less explored. In present study, we found that rasfonin, which isolated from Talaromyces sp. 3656-A1 and was a fungal natural product, activated both caspase-dependent apoptosis and autophagy in ACHN, a renal carcinoma cell line. Knockdown of Raptor decreased both rasfonin-induced autophagic flux and PARP-1 cleavage, and in contrast, Rictor silencing increased apoptosis concomitantly enhancing rasfonin-induced autophagy. Unexpectedly, API-2, which was widely used as an inhibitor of Akt, promoted rasfonin-dependent autophagy in Raptor-depleted but not Rictor-deprived cells. Collectively, these results demonstrated that Raptor and Rictor could play a distinctly regulatory role in rasfonin-enhanced autophagy and apoptosis.
雷帕霉素靶蛋白（mTOR）复合物的关键组成部分 Raptor 和 Rictor 在介导自噬中起着至关重要的作用。与 mTOR 不同，Raptor 或 Rictor 在自噬过程调节中的调控作用相对较少被探索。在本研究中，我们发现从 Talaromyces sp. 3656-A1 中分离出的 rasfonin 是一种真菌天然产物，能够激活肾癌细胞系 ACHN 中的 caspase 依赖性细胞凋亡和自噬。Raptor 的敲低减少了 rasfonin 诱导的自噬通量和 PARP-1 切割，相反，Rictor 的沉默增加了细胞凋亡，同时增强了 rasfonin 诱导的自噬。出乎意料的是，广泛用作 Akt 抑制剂的 API-2 在 Raptor 耗尽的细胞中促进了 rasfonin 依赖性自噬，但在 Rictor 耗尽的细胞中没有促进。总的来说，这些结果表明 Raptor 和 Rictor 可以在 rasfonin 增强的自噬和细胞凋亡中发挥明显的调节作用。
