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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Rodriguez, Karl A.^1,2  Osmulski, Pawel A.^1,3  Pierce, Anson⁴  Weintraub, Susan T.⁶  Gaczynska, Maria^1,3  Buffenstein, Rochelle^1,2,5 

[1] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Aging & Longev Studies, San Antonio, TX 78245 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA

[4] Univ Texas Med Branch, Dept Biochem & Mol Biol, Mitchell Ctr Neurodegenerat Dis, Galveston, TX 77555 USA

[5] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA

关键词: Proteasome;    Heat shock protein;    Naked mole-rat;    Protease inhibitor;    Protein degradation;    Aging;   

DOI  :  10.1016/j.bbadis.2014.07.005

来源: Elsevier

【 摘 要 】

The naked mole-rat maintains robust proteostasis and high levels of proteasome-mediated proteolysis for most of its exceptional (similar to 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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free