RRC ID 49535
著者 Liu Y, Mattila J, Ventelä S, Yadav L, Zhang W, Lamichane N, Sundström J, Kauko O, Grénman R, Varjosalo M, Westermarck J, Hietakangas V.
タイトル PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of Ribosomal Gene Expression.
ジャーナル Dev. Cell
Abstract 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.
巻・号 43(2)
ページ 240-252.e5
公開日 2017-10-25
DOI 10.1016/j.devcel.2017.09.022
PII S1534-5807(17)30781-5
PMID 29065309
MeSH Animals Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Nucleolus / metabolism* Chromatin / genetics DNA, Ribosomal / genetics Drosophila / genetics Drosophila / growth & development Drosophila / metabolism Food* Gene Expression Regulation* Head and Neck Neoplasms / genetics Head and Neck Neoplasms / metabolism Head and Neck Neoplasms / pathology* Humans Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phosphorylation Prognosis RNA Polymerase I / metabolism RNA, Ribosomal / genetics Ribosomes / genetics* Signal Transduction Survival Rate TOR Serine-Threonine Kinases / metabolism Transcription, Genetic
ショウジョウバエ 6751R-1 6751R-3