TIF-IA: An oncogenic target of pre-ribosomal RNA synthesis

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• 作者：Rui Jin^a ; Wei Zhou^a ; ^b ; ^{wzhou2@emory.edu}
• 关键词：TIF-IA ; Transcription factor ; Pre-ribosomal RNA synthesis ; RNA polymerase I ; Oncogenic kinases ; Targeted therapy
• 刊名：Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：1866
• 期：2
• 页码：189-196
• 全文大小：521 K
• 卷排序：1866

文摘

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.