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首页> 外文期刊>Cell cycle >REGgamma proteasome activator is involved in the maintenance of chromosomal stability.
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REGgamma proteasome activator is involved in the maintenance of chromosomal stability.

机译：REGgamma蛋白酶体激活剂参与维持染色体的稳定性。

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摘要

REGgamma is a member of the 11S regulatory particle that activates the 20S proteasome. Studies in REGgamma deficient mice indicated an additional role for this protein in cell cycle regulation and proliferation control. In this paper we demonstrate that REGgamma protein is equally expressed throughout the cell cycle, but undergoes a distinctive subcellular localization at mitosis. Thus, while in interphase cells REGgamma is nuclear, in telophase cells it localizes on chromosomes, suggesting a role in mitotic progression. Furthermore, we found that REGgamma overexpression weakens the mitotic arrest induced by spindle damage, allowing premature exit from mitosis, whereas REGgamma depletion has the opposite effect, thus reflecting a new REGgamma function, unrelated to its role as proteasome activator. Additionally, we found that primary cells from REGgamma-/- mice and human fibroblasts with depleted expression of REGgamma or overexpressing a dominant negative mutant unable to activate the 20S proteasome, demonstrated a marked aneuploidy (chromosomal gains and losses), supernumerary centrosomes and multipolar spindles. These findings thus underscore a previously uncharacterized function of REGgamma in centrosome and chromosomal stability maintenance.
机译：REGgamma是激活20S蛋白酶体的11S调控颗粒的成员。对REGgamma缺陷型小鼠的研究表明，该蛋白在细胞周期调控和增殖控制中具有额外的作用。在本文中，我们证明REGgamma蛋白在整个细胞周期中均表达，但在有丝分裂时经历了独特的亚细胞定位。因此，尽管在相间细胞中REGgamma是核的，但在末期细胞中它位于染色体上，提示在有丝分裂的进程中起作用。此外，我们发现REGgamma的过表达减弱了纺锤体损伤诱导的有丝分裂停滞，允许过早退出有丝分裂，而REGgamma的消耗却有相反的作用，从而反映了新的REGgamma的功能，与它作为蛋白酶体激活剂的作用无关。此外，我们发现来自REGgamma //-小鼠和成纤维细胞的REGgamma表达减少或过度表达显性负突变体的原代细胞不能激活20S蛋白酶体，表现出明显的非整倍性（染色体得失），超数中心体和多极纺锤体。因此，这些发现强调了REGgamma以前在中心体和染色体稳定性维持中未表征的功能。

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