The Aryl Hydrocarbon Receptor Undergoes Chaperone-Mediated Autophagy in Triple-Negative Breast Cancer Cells.

The Aryl Hydrocarbon Receptor Undergoes Chaperone-Mediated Autophagy in Triple-Negative Breast Cancer Cells.
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DOI:
10.3390/ijms22041654
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发表时间:
2021-02-06
影响因子:
5.6
通讯作者:
Chan WK
Chan WK
中科院分区:
生物学2区
文献类型:
--
作者:
Chen J;Yang Y;Russu WA;Chan WK

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芳香烃受体(AHR)是一种配体激活的信号分子,在许多细胞类型中表达,包括三阴性和非三阴性乳腺癌细胞。它会影响乳腺癌的生长,并与雌激素受体信号传导相互干扰。通常,这种受体在配体活化后不久通过26 S蛋白酶体降解。在这里,我们报告说,AHR经历伴侣介导的自噬在MDA-MB-468三阴性乳腺癌细胞。AHR的这种溶酶体降解表现出以下特征:(1)它由6氨基烟酰胺、饥饿和哌嗪嘧啶化合物Q18触发;(2)在非三阴性乳腺癌细胞中未观察到(3)能被孕激素受体B抑制,但不能被雌激素受体α抑制;(4)它可以被氯喹逆转,但不能被MG 132逆转;(5)它需要LAMP 2A;(6)它涉及AHR-HSC 70和AHR-LAMP 2A相互作用。位于人AHR的氨基酸558处的NEKFF序列似乎是分子伴侣介导的自噬的KFERQ样基序,负责LAMP 2A介导的AHR蛋白降解。
The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule expressed in many cell types, including triple-negative and non-triple-negative breast cancer cells. It affects breast cancer growth and crosstalk with estrogen receptor signaling. Normally, this receptor is degraded shortly after ligand activation via the 26S proteasome. Here, we report that AHR undergoes chaperone-mediated autophagy in MDA-MB-468 triple-negative breast cancer cells. This lysosomal degradation of AHR exhibits the following characteristics: (1) it is triggered by 6 amino-nicotinamide, starvation, and piperazinylpyrimidine compound Q18; (2) it is not observed in non-triple-negative breast cancer cells (MCF-7, T47D, and MDA-MB-361); (3) it can be inhibited by progesterone receptor B but not estrogen receptor alpha; (4) it can be reversed by chloroquine but not MG132; (5) it requires LAMP2A; and (6) it involves AHR-HSC70 and AHR-LAMP2A interactions. The NEKFF sequence localized at amino acid 558 of human AHR appears to be a KFERQ-like motif of chaperone-mediated autophagy, responsible for the LAMP2A-mediated AHR protein degradation.
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伴侣介导的自噬的时代的到来。
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