CRYPTOCHROMES promote daily protein homeostasis.
CRYPTOCHROMES promote daily protein homeostasis.
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DOI：
10.15252/embj.2021108883
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发表时间：
2022-01-04
期刊：
影响因子：
--
通讯作者：
O'Neill JS
中科院分区：
文献类型：
--
作者：
Wong DCS;Seinkmane E;Zeng A;Stangherlin A;Rzechorzek NM;Beale AD;Day J;Reed M;Peak-Chew SY;Styles CT;Edgar RS;Putker M;O'Neill JS
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，由线粒体依赖性转录反馈抑制的每日循环驱动。为了验证这一点，我们使用定量质谱法在恒定条件下比较野生型和CRY缺陷型成纤维细胞。在CRY缺陷细胞中，我们发现蛋白质，磷酸肽和K+丰度的时间变化至少与野生型对照一样大。最引人注目的是，任一基因型内的时间变化程度远小于WT和CRY缺陷细胞之间蛋白质组组成的总体差异。CRY缺陷细胞和组织中的这种蛋白质组失衡与对蛋白毒性应激的易感性增加有关，这会损害昼夜节律的稳健性，并可能导致CRY缺陷小鼠的广泛表型。我们认为，CRY蛋白的各种转录和翻译后功能最终起作用以维持蛋白质和渗透压稳态对抗日常干扰，而不是产生蛋白质组组成的大规模每日变化。线粒体对昼夜蛋白质组振荡不是必需的，但在蛋白质和渗透稳态的时间调节中起关键作用。
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 used quantitative mass spectrometry to compare wild‐type and CRY‐deficient fibroblasts under constant conditions. In CRY‐deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild‐type controls. Most strikingly, the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY‐deficient cells. This proteome imbalance in CRY‐deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide‐ranging phenotypes of CRY‐deficient mice. Rather than generating large‐scale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post‐translational functions of CRY proteins ultimately act to maintain protein and osmotic homeostasis against daily perturbation. CRYPTOCHROMES are not essential for circadian proteome oscillations but play a crucial role in the temporal regulation of protein and osmotic homeostasis.
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影响因子：
5.4
作者：
Bulik S;Holzhütter HG;Berndt N
通讯作者：
Berndt N
DOI：
10.1073/pnas.1612917113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Chiou, Yi-Ying;Yang, Yanyan;Sancar, Aziz
通讯作者：
Sancar, Aziz
影响因子：
7
作者：
Cenik C;Cenik ES;Byeon GW;Grubert F;Candille SI;Spacek D;Alsallakh B;Tilgner H;Araya CL;Tang H;Ricci E;Snyder MP
通讯作者：
Snyder MP
影响因子：
7
作者：
Collins EJ;Cervantes-Silva MP;Timmons GA;O'Siorain JR;Curtis AM;Hurley JM
通讯作者：
Hurley JM
DOI：
10.1152/ajpendo.00512.2012
发表时间：
2013-05-01
影响因子：
5.1
作者：
Barclay, Johanna L.;Shostak, Anton;Oster, Henrik
通讯作者：
Oster, Henrik