当前位置: X-MOL 学术J. Cell Sci. › 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.)
Role of a versatile peptide motif controlling Hox nuclear export and autophagy in the Drosophila fat body.
Journal of Cell Science ( IF 4 ) Pub Date : 2020-09-23 , DOI: 10.1242/jcs.241943
Marilyne Duffraisse 1 , Rachel Paul 1 , Julie Carnesecchi 2 , Bruno Hudry 3 , Agnes Banreti 3 , Jonathan Reboulet 1 , Leiore Ajuria 1 , Ingrid Lohmann 2 , Samir Merabet 4
Affiliation  

Marilyne Duffraisse, Rachel Paul, Julie Carnesecchi, Bruno Hudry, Agnes Banreti, Jonathan Reboulet, Leiore Ajuria, Ingrid Lohmann, and Samir Merabet

Hox proteins are major regulators of embryonic development, acting in the nucleus to regulate the expression of their numerous downstream target genes. By analyzing deletion forms of the Drosophila Hox protein Ultrabithorax (Ubx), we identified the presence of an unconventional nuclear export signal (NES) that overlaps with a highly conserved motif originally described as mediating the interaction with the PBC proteins, a generic and crucial class of Hox transcriptional cofactors that act in development and cancer. We show that this unconventional NES is involved in the interaction with the major exportin protein CRM1 (also known as Embargoed in flies) in vivo and in vitro. We find that this interaction is tightly regulated in the Drosophila fat body to control the autophagy-repressive activity of Ubx during larval development. The role of the PBC interaction motif as part of an unconventional NES was also uncovered in other Drosophila and human Hox proteins, highlighting the evolutionary conservation of this novel function. Together, our results reveal the extreme molecular versatility of a unique short peptide motif for controlling the context-dependent activity of Hox proteins both at transcriptional and non-transcriptional levels.



中文翻译:

控制果蝇脂肪体中 Hox 核输出和自噬的多功能肽基序的作用。

Marilyne Duffraisse、Rachel Paul、Julie Carnesecchi、Bruno Hudry、Agnes Banreti、Jonathan Reboulet、Leiore Ajuria、Ingrid Lohmann 和 Samir Merabet

Hox 蛋白是胚胎发育的主要调节因子,在细胞核中发挥作用,调节其众多下游靶基因的表达。通过分析果蝇Hox 蛋白 Ultrabithorax (Ubx) 的缺失形式,我们发现了非常规核输出信号 (NES) 的存在,该信号与高度保守的基序重叠,该基序最初被描述为介导与 PBC 蛋白的相互作用,PBC 蛋白是一类通用且关键的蛋白Hox 转录辅助因子在发育和癌症中发挥作用。我们证明,这种非常规的 NES在体内体外参与与主要输出蛋白 CRM1(也称为果蝇禁运蛋白)的相互作用。我们发现这种相互作用在果蝇脂肪体中受到严格调节,以控制幼虫发育过程中 Ubx 的自噬抑制活性。PBC 相互作用基序作为非常规 NES 一部分的作用也在其他果蝇和人类 Hox 蛋白中被发现,突出了这种新功能的进化保守性。总之,我们的结果揭示了独特的短肽基序在转录和非转录水平上控制 Hox 蛋白的上下文依赖性活性的极端分子多功能性。

更新日期:2020-10-02
down
wechat
bug