PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression

被引：25

作者：

Liu, Ying ^{[1
,2
]}

Mattila, Jaakko ^{[1
,2
,10
]}

Ventela, Sami ^{[3
,4
]}

Yadav, Leena ^{[2
]}

Zhang, Wei ^{[1
,2
,11
]}

Lamichane, Nicole ^{[1
,2
]}

Sundstrom, Jari ^{[5
,6
]}

Kauko, Otto ^{[3
,4
,5
]}

Grenman, Reidar ^{[7
,8
,9
]}

Varjosalo, Markku ^{[2
]}

Westermarck, Jukka ^{[3
,4
,5
]}

Hietakangas, Ville ^{[1
,2
]}

机构：

[1] Univ Helsinki, Dept Biosci, Helsinki 00790, Finland

[2] Univ Helsinki, Inst Biotechnol, Helsinki 00790, Finland

[3] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku, Finland

[4] Abo Akad Univ, FIN-20520 Turku, Finland

[5] Univ Turku, Dept Pathol, FIN-20520 Turku, Finland

[6] Turku Univ Hosp, Dept Pathol, FIN-20520 Turku, Finland

[7] Univ Turku, Dept Otorhinolaryngol Head & Neck Surg, Turku 20521, Finland

[8] Univ Turku, Dept Med Biochem & Genet, Turku 20521, Finland

[9] Turku Univ Hosp, Turku 20521, Finland

[10] DKFZ, D-69120 Heidelberg, Germany

[11] Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210014, Jiangsu, Peoples R China

来源：

DEVELOPMENTAL CELL | 2017年 / 43卷 / 02期

基金：

欧洲研究理事会; 芬兰科学院;

关键词：

RNA-POLYMERASE-I; CELL-GROWTH; TRANSCRIPTION; PROTEIN; CHROMATIN; YEAST; MTOR; INSULIN; KINASE; CANCER;

D O I：

10.1016/j.devcel.2017.09.022

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ribosome biogenesis regulates animal growth and is controlled by nutrient-responsive mTOR signaling. How ribosome biogenesis is regulated during the developmental growth of animals and how nutrient-responsive signaling adjusts ribosome biogenesis in this setting have remained insufficiently understood. We uncover PWP1 as a chromatin-associated regulator of developmental growth with a conserved role in RNA polymerase I (Pol I)-mediated rRNA transcription. We further observed that PWP1 epigenetically maintains the rDNA loci in a transcription-competent state. PWP1 responds to nutrition in Drosophila larvae via mTOR signaling through gene expression and phosphorylation, which controls the nucleolar localization of dPWP1. Our data further imply that dPWP1 acts synergistically with mTOR signaling to regulate the nucleolar localization of TFIIH, a known elongation factor of Pol I. Ribosome biogenesis is often deregulated in cancer, and we demonstrate that high PWP1 levels in human head and neck squamous cell carcinoma tumors are associated with poor prognosis.

引用

页码：240 / +

页数：18

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