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分选连接蛋白 27 作为 G 蛋白偶联受体循环的潜在靶点用于癌症治疗(综述)。

Sorting Nexin 27 as a potential target in G protein‑coupled receptor recycling for cancer therapy (Review).

机构信息

Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Department of Infectious Disease, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):1779-1786. doi: 10.3892/or.2020.7766. Epub 2020 Sep 14.

Abstract

G protein‑coupled receptors (GPCRs) are the largest family of membrane receptors and activate several downstream signaling pathways involved in numerous physiological cellular processes. GPCRs are usually internalized and desensitized by intracellular signals. Numerous studies have shown that several GPCRs interact with sorting nexin 27 (SNX27), a cargo selector of the retromer complex, and are recycled from endosomes to the plasma membrane. Recycled GPCRs usually contain specific C‑terminal postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) binding motifs, which are specifically recognized by SNX27, and return to the cell surface as functionally naïve receptors. Aberrant endosome‑to‑membrane recycling of GPCRs mediated by SNX27 may serve a critical role in cancer growth and development. Therefore, SNX27 may be a novel target for cancer therapies.

摘要

G 蛋白偶联受体(GPCRs)是最大的膜受体家族,可激活多种下游信号通路,参与众多生理细胞过程。GPCR 通常通过细胞内信号被内化和脱敏。许多研究表明,几种 GPCR 与分选连接蛋白 27(SNX27)相互作用,SNX27 是再循环体复合物的货物分选器,从内体再循环到质膜。再循环的 GPCR 通常含有特定的 C 末端突触后密度蛋白 95/离散蛋白/Discs 大蛋白/Zonula occludens 1(PDZ)结合基序,这些基序被 SNX27 特异性识别,并作为功能上未成熟的受体返回细胞表面。由 SNX27 介导的 GPCR 内体到质膜的异常再循环可能在癌症的生长和发展中起关键作用。因此,SNX27 可能是癌症治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f326/7551096/500f0ec32d52/OR-44-05-1779-g00.jpg

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