当前位置: X-MOL 学术Mol. Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Translational Repression of G3BP in Cancer and Germ Cells Suppresses Stress Granules and Enhances Stress Tolerance.
Molecular Cell ( IF 16.0 ) Pub Date : 2020-07-20 , DOI: 10.1016/j.molcel.2020.06.037
Anna K Lee 1 , Jonathon Klein 1 , Klementina Fon Tacer 1 , Tessa Lord 2 , Melissa J Oatley 2 , Jon M Oatley 2 , Shaina N Porter 1 , Shondra M Pruett-Miller 1 , Elena B Tikhonova 3 , Andrey L Karamyshev 3 , Yong-Dong Wang 1 , Peiguo Yang 1 , Ane Korff 1 , Hong Joo Kim 1 , J Paul Taylor 4 , Patrick Ryan Potts 1
Affiliation  

Stress granules (SGs) are membrane-less ribonucleoprotein condensates that form in response to various stress stimuli via phase separation. SGs act as a protective mechanism to cope with acute stress, but persistent SGs have cytotoxic effects that are associated with several age-related diseases. Here, we demonstrate that the testis-specific protein, MAGE-B2, increases cellular stress tolerance by suppressing SG formation through translational inhibition of the key SG nucleator G3BP. MAGE-B2 reduces G3BP protein levels below the critical concentration for phase separation and suppresses SG initiation. Knockout of the MAGE-B2 mouse ortholog or overexpression of G3BP1 confers hypersensitivity of the male germline to heat stress in vivo. Thus, MAGE-B2 provides cytoprotection to maintain mammalian spermatogenesis, a highly thermosensitive process that must be preserved throughout reproductive life. These results demonstrate a mechanism that allows for tissue-specific resistance against stress and could aid in the development of male fertility therapies.



中文翻译:

G3BP在癌细胞和生殖细胞中的翻译抑制可抑制应激颗粒并增强应激耐受性。

应激颗粒(SGs​​)是无膜核糖核蛋白缩合物,可通过相分离响应各种应激刺激而形成。SGs是应付急性应激的保护机制,但是持续性SGs具有与几种与年龄有关的疾病有关的细胞毒性作用。在这里,我们证明了睾丸特异性蛋白MAGE-B2通过对关键SG成核剂G3BP的翻译抑制来抑制SG的形成,从而增加了细胞对压力的耐受性。MAGE-B2可将G3BP蛋白水平降低至相分离的临界浓度以下,并抑制SG引发。MAGE-B2小鼠直系同源基因的敲除或G3BP1的过表达赋予雄性种系对体内热应激的超敏性。因此,MAGE-B2提供了细胞保护作用,以维持哺乳动物的精子发生,这是一个高度热敏的过程,必须在整个生殖生命中保存下来。这些结果证明了一种机制,该机制允许组织对压力的特异性抗性,并有助于男性生殖疗法的发展。

更新日期:2020-08-20
down
wechat
bug