期刊
CELL CYCLE
卷 17, 期 1, 页码 92-101出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2017.1403685
关键词
ribosome biogenesis; HEATR1; p53; ribosome biogenesis stress; cancer
类别
资金
- Grant Agency of the Czech Republic [17-14743S, 17-25976S]
- MEYS CR [CZ.02.1.01/0.0/0.0/16_013/0001775 Czech-BioImaging]
- Czech National Program of Sustainability [LO1304]
- UP [IGA_LF_2017_002]
- Danish Cancer Society
- Danish Council for Independent Research
- Swedish Research Council
- CancerFonden
- Lundbeck Foundation
- Danish National Research Foundation (Center of Excellence, project CARD)
- Czech Science Foundation (GACR) [17-14743S]
- Lundbeck Foundation [R93-2011-8990] Funding Source: researchfish
- The Danish Cancer Society [R124-A7785] Funding Source: researchfish
Ribosome biogenesis is an energy consuming process which takes place mainly in the nucleolus. By producing ribosomes to fuel protein synthesis, it is tightly connected with cell growth and cell cycle control. Perturbation of ribosome biogenesis leads to the activation of p53 tumor suppressor protein promoting processes like cell cycle arrest, apoptosis or senescence. This ribosome biogenesis stress pathway activates p53 through sequestration of MDM2 by a subset of ribosomal proteins (RPs), thereby stabilizing p53. Here, we identify human HEATR1, as a nucleolar protein which positively regulates ribosomal RNA (rRNA) synthesis. Downregulation of HEATR1 resulted in cell cycle arrest in a manner dependent on p53. Moreover, depletion of HEATR1 also caused disruption of nucleolar structure and activated the ribosomal biogenesis stress pathway - RPL5 / RPL11 dependent stabilization and activation of p53. These findings reveal an important role for HEATR1 in ribosome biogenesis and further support the concept that perturbation of ribosome biosynthesis results in p53-dependent cell cycle checkpoint activation, with implications for human pathologies including cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据