CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis
CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis
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DOI：
10.1101/2020.05.16.099556
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发表时间：
2020-05
期刊：
影响因子：
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通讯作者：
David C. S. Wong;Estere Seinkmane;Alessandra Stangherlin;Aiwei Zeng;N. Rzechorzek;Andrew D. Beale;
中科院分区：
文献类型：
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作者：
David C. S. Wong;Estere Seinkmane;Alessandra Stangherlin;Aiwei Zeng;N. Rzechorzek;Andrew D. Beale;
大多数哺乳动物细胞功能的日常组织归因于生物钟控制的蛋白质表达的昼夜节律调节，其由线粒体色素依赖性转录反馈抑制的每日循环驱动。为了验证这一点，我们比较了野生型和β-淀粉样蛋白缺乏的成纤维细胞的昼夜蛋白质组和磷酸化蛋白质组。令人惊讶的是，β-淀粉样蛋白缺乏的细胞表现出两倍的昼夜节律调节蛋白，磷酸肽，和K+运输增加。这伴随着细胞蛋白质组整体的广泛重塑，包括磷酸酶和蛋白酶体亚基表达的减少。这些适应性改变使得β-D-1缺陷细胞对应激更敏感，这可能是它们昼夜节律稳健性降低的原因，并有助于β-D-1缺陷小鼠的广泛表型。我们认为，CRY最终的功能是抑制，而不是产生，细胞蛋白质丰度的日常节奏，从而维持蛋白质和渗透压稳态。
The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we compared the circadian proteome and phosphoproteome of wild type and CRY-deficient fibroblast cells. Strikingly, CRY-deficient cells showed a two-fold increase in circadian-regulated proteins, phosphopeptides, and K+ transport. This was accompanied by extensive remodelling of the cellular proteome overall, including reduced phosphatase and proteasome subunit expression. These adaptations rendered CRY-deficient cells more sensitive to stress, which may account for their reduced circadian robustness and contribute to the wide-ranging phenotypes of CRY-deficient mice. We suggest that CRY ultimately functions to suppress, rather than generate, daily rhythms in cellular protein abundance, thereby maintaining protein and osmotic homeostasis.