A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition.

A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition.
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来自裸鼹鼠的胞质蛋白因子可激活其他物种的蛋白酶体并保护它们免受抑制。

DOI:
10.1016/j.bbadis.2014.07.005
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发表时间:
2014
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Buffenstein,Rochelle
Buffenstein,Rochelle
中科院分区:
--
文献类型:
--
作者:
Rodriguez,KarlA;Osmulski,PawelA;Pierce,Anson;Weintraub,SusanT;Gaczynska,Maria;Buffenstein,Rochelle

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裸鼹鼠在其大部分特殊寿命(约31年)内保持稳健的蛋白质稳态和高水平的蛋白酶体介导的蛋白质水解。在这里,我们报告说,高活性的蛋白酶体从裸鼹鼠肝脏抵抗衰减的一套不同的蛋白酶体特异性小分子抑制剂。此外,小鼠,人类和酵母蛋白酶体暴露于蛋白酶体耗尽,裸鼹鼠-大鼠胞质组分,概括了观察到的抑制抗性,哺乳动物蛋白酶体也显示出增加的活性。凝胶过滤结合质谱和原子力显微镜表明,这些性状是由一个蛋白质因子,驻留在胞质溶胶的支持。该因子与蛋白酶体相互作用并调节其活性。虽然热休克蛋白72 kDa(HSP 72)和热休克蛋白40 kDa(细菌DNAJ 1的同源物)(HSP 40(Hdj 1))是该因子的组成部分,但观察到的现象,如增加肽酶活性和防止抑制不能与任何已知的伴侣蛋白功能相协调。这种新的功能可能有助于裸鼹鼠特殊的蛋白质稳态,并使其成功地对抗衰老。
The naked mole-rat maintains robust proteostasis and high levels of proteasome-mediated proteolysis for most of its exceptional (~ 31 years) life span. Here, we report that the highly active proteasome from the naked mole-rat liver resists attenuation by a diverse suite of proteasome-specific small molecule inhibitors. Moreover, mouse, human, and yeast proteasomes exposed to the proteasome-depleted, naked mole-rat cytosolic fractions, recapitulate the observed inhibition resistance, and mammalian proteasomes also show increased activity. Gel filtration coupled with mass spectrometry and atomic force microscopy indicates that these traits are supported by a protein factor that resides in the cytosol. This factor interacts with the proteasome and modulates its activity. Although Heat shock protein 72 kDa (HSP72) and Heat shock protein 40 kDa (Homolog of bacterial DNAJ1) (HSP40(Hdj1)) are among the constituents of this factor, the observed phenomenon, such as increasing peptidase activity and protecting against inhibition cannot be reconciled with any known chaperone functions. This novel function may contribute to the exceptional protein homeostasis in the naked mole-rat and allow it to successfully defy aging.
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