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一个PARP14/TARG1-调节的RACK1MARylation周期驱动了卵巢癌细胞中的压力颗粒动力学
Sridevi Challa1,2, Tulip Nandu1, Hyung Bum Kim1,3
1Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
bioRxiv : the preprint server for biology
|October 24, 2023
概括
通过PARP14对RACK1的单基化 (MARylation) 调节卵巢癌中的压力颗粒和翻译. 抑制这种途径会阻止癌细胞的生长,从而成为潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 生物化学 生化学
背景情况:
- 单基ADP-ribosyl) 化 (MARylation) 越来越多地被认为是它在调节核糖体功能和蛋白质转化中的作用.
- RACK1是核糖体的关键组成部分,涉及各种细胞过程.
研究的目的:
- 为了研究RACK1 MARylation在卵巢癌中的作用.
- 为了确定参与RACK1 MARylation和deMARylation的酶.
- 探索准这种途径的治疗潜力.
主要方法:
- 卵巢癌细胞培养和体内模型.
- 在RACK上MARIlated残留物的识别1.1.
- 对PARP14和TARG1.1的酶活性测定.
- 西方涂抹和免疫沉.
- 翻译和细胞生长的评估.
主要成果:
- 在卵巢癌细胞中,RACK1通过PARP14在三个酸性残留物上被MARylated.
- RACK1 MARylation对于压力颗粒的形成和与特定蛋白质的同定位至关重要.
- 马里化减少了关键癌症相关的mRNA,如AKT的翻译,并促进卵巢癌细胞的生长.
- PARP14 抑制或 RACK1 突变阻断了这些效应.
- TARG1 脱MARylates RACK1,导致应力颗粒分解和翻译恢复.
结论:
- 一个涉及RACK1,PARP14和TARG1的新型MARylation-dependent通路调节了卵巢癌中的压力颗粒动态和翻译.
- 这一途径代表了卵巢癌治疗的有希望的治疗标.
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