title: TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters.
abstract: Cells control their metabolism through modulating the anabolic and catabolic pathways. TP53INP2/DOR (tumor protein p53 inducible nuclear protein 2), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of TP53INP2 in protein synthesis, a major biosynthetic and energy-consuming anabolic process. TP53INP2 localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of TP53INP2 with the ribosomal DNA (rDNA), when exclusion of TP53INP2 from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of TP53INP2 also impaired the association of the POLR1/RNA polymerase I preinitiation complex (PIC) with rDNA. Further, TP53INP2 interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of TP53INP2 in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wan
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shou
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: You
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shou
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.|b Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhou
authors.affiliation: a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.|b Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D001343:Autophagy / Q000235:genetics*; D004275:DNA, Ribosomal / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004275:DNA, Ribosomal; D009687:Nuclear Proteins; C501283:TP53INP2 protein, human; D012318:RNA Polymerase I
keywords: TP53INP2/DOR; autophagy; nucleolus; preinitiation complex; rDNA