title: TIF-IA: An oncogenic target of pre-ribosomal RNA synthesis.
abstract: Cancer cells devote the majority of their energy consumption to ribosome biogenesis, and pre-ribosomal RNA transcription accounts for 30-50% of all transcriptional activity. This aberrantly elevated biological activity is an attractive target for cancer therapeutic intervention if approaches can be developed to circumvent the development of side effects in normal cells. TIF-IA is a transcription factor that connects RNA polymerase I with the UBF/SL-1 complex to initiate the transcription of pre-ribosomal RNA. Its function is conserved in eukaryotes from yeast to mammals, and its activity is promoted by the phosphorylation of various oncogenic kinases in cancer cells. The depletion of TIF-IA induces cell death in lung cancer cells and mouse embryonic fibroblasts but not in several other normal tissue types evaluated in knock-out studies. Furthermore, the nuclear accumulation of TIF-IA under UTP down-regulated conditions requires the activity of LKB1 kinase, and LKB1-inactivated cancer cells are susceptible to cell death under such stress conditions. Therefore, TIF-IA may be a unique target to suppress ribosome biogenesis without significantly impacting the survival of normal tissues.
authors.affiliation: Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Pathology and Laboratory Medicine and Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: wzhou2@emory.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012322:RNA Precursors / Q000096:biosynthesis*
chemical_list: D035463:Pol1 Transcription Initiation Complex Proteins; D012322:RNA Precursors; C428423:RRN3 protein, human
keywords: Oncogenic kinases; Pre-ribosomal RNA synthesis; RNA polymerase I; TIF-IA; Targeted therapy; Transcription factor