title: mTOR-dependent transcriptional repression of Pdcd4 tumor suppressor in lung cancer cells.
abstract: Programmed cell death 4 (Pdcd4) tumor suppressor is frequently lost in tumors of various origins including lung cancer, and its loss contributes to tumor progression. However molecular mechanisms underlying Pdcd4 suppression in lung cancer cells remain largely unexplored. Here we investigated molecular mechanisms of Pdcd4 suppression in lung cancer cells. Besides enhanced mTOR-dependent proteasomal degradation of Pdcd4 protein, we found that Pdcd4 transcription is negatively regulated by mTOR signaling, and localized cis-acting element in Pdcd4 promoter responsible for this effect. In conclusion, we described a novel molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR signaling-dependent transcriptional repression of Pdcd4.
authors: Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov str., Moscow 119334, Russia.
authors: P N
authors: PN
authors: Vikhreva
authors: Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov str., Moscow 119334, Russia.
authors: M V
authors: MV
authors: Shepelev
authors: Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov str., Moscow 119334, Russia. Electronic address: igorvk@igb.ac.ru.
authors: I V
authors: IV
authors: Korobko
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex
keywords: Lung cancer cells; Pdcd4; Transcriptional suppression; Tumor suppressor; mTOR