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首页> 外文期刊>Journal of Cellular Physiology >Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells
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Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells

机译：Phosphorylation-regulated退化肿瘤抑制的PED的形式即使伴娘在肺癌细胞自噬

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摘要

PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms.
机译：PED / PEA-15死亡效应域(d)的家庭成员与各种对细胞生长的影响和新陈代谢。PED在癌症中的作用,旨在寻找新的PED扶少团团员。我们确定了HSC70(热休克蛋白质同源70 kda)——等流程——参与即使伴娘自噬(CMA)一个PED-interacting蛋白质。两个CMA-like图案(即KFERQ),其中一个坐落在一个磷酸化网站,吗证明是一个真正的CMA衬底下车和磷酸化的第一个例子修改HSC70访问的能力KFERQ-like主题和目标的蛋白质溶酶体降解。开关从肿瘤抑制功能肿瘤推广,我们表明HSC70非磷酸化形式优先目标PED CMA。差异CMA活动最大的特点类型的癌症细胞增强肿瘤形成PED的平衡功能对肿瘤转移推广。针对治疗潜力的概念CMA在癌症,抑制自噬途径可以帮助恢复生理的比率PED形式。

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