HSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here, we described a novel role of HSP90 in the cytosolic compartmentalization of metabolic pathways in proliferating cancer cells. We found that HSP90 assists in the organization of metabolic enzymes into non-membrane-bound functional compartments termed metabosomes. Under experimental conditions that conserved the cellular proteostasis, we demonstrated that the compartmentalizing activity of HSP90 is critical to sustain the coordinated synthesis of multiple metabolites required for energy production, maintenance of the cellular biomass and secretion of immunometabolites. Conversely, inhibition of the nucleating capacity of HSP90 modified the topology of cytosolic metabosomes before protein degradation was apparent decreasing the efficiency of MYC-driven metabolic pathways. Inhibition of HSP90 decreases cancer metabolism in B-cell lymphoma cells and patients providing a novel mechanism of activity for this class of drugs.

中文翻译：

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HSP90促进B细胞淋巴瘤代谢的致癌性改变

HSP90对于维持细胞蛋白变性至关重要。在癌细胞中，HSP90也成为稳定多蛋白复合物（包括信号传导途径和转录复合物）的成核位点。在这里，我们描述了HSP90在增殖癌细胞的代谢途径的胞质区室化中的新作用。我们发现，HSP90有助于将代谢酶组织到被称为代谢体的非膜结合功能区室中。在保存细胞蛋白水解的实验条件下，我们证明了HSP90的区室化活性对于维持能量产生，维持细胞生物量和免疫代谢产物分泌所需的多种代谢物的协调合成至关重要。反过来，抑制HSP90的成核能力可以在蛋白质降解明显之前降低胞质代谢体的拓扑结构，从而降低MYC驱动的代谢途径的效率。抑制HSP90会降低B细胞淋巴瘤细胞中的癌症代谢，患者为此类药物提供了新的活性机制。