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  • AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing.

AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing.

Nature communications (2021-08-01)
Georgios I Laliotis, Evangelia Chavdoula, Maria D Paraskevopoulou, Abdul Kaba, Alessandro La Ferlita, Satishkumar Singh, Vollter Anastas, Keith A Nair, Arturo Orlacchio, Vasiliki Taraslia, Ioannis Vlachos, Marina Capece, Artemis Hatzigeorgiou, Dario Palmieri, Christos Tsatsanis, Salvatore Alaimo, Lalit Sehgal, David P Carbone, Vincenzo Coppola, Philip N Tsichlis
摘要

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficient U2AF2 splice variant. Here, we show that exon 2 inclusion in the U2AF2 mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes. The exon 2-deficient U2AF2 mRNA encodes a Serine-Arginine-Rich (RS) domain-deficient U2AF65, which is defective in CDCA5 pre-mRNA processing. This results in downregulation of the CDCA5-encoded protein Sororin, a phosphorylation target and regulator of ERK, G2/M arrest and impaired cell proliferation and tumor growth. Analysis of human lung adenocarcinomas, confirmed activation of the pathway in EGFR-mutant tumors and showed that pathway activity correlates with tumor stage, histologic grade, metastasis, relapse after treatment, and poor prognosis.

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氯仿, contains 100-200 ppm amylenes as stabilizer, ≥99.5%
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杜氏改良 Eagle 培养基 - 高葡萄糖, With 4500 mg/L glucose, L-glutamine, and sodium bicarbonate, without sodium pyruvate, liquid, sterile-filtered, suitable for cell culture
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甲醛 溶液, for molecular biology, 36.5-38% in H2O
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柠檬酸盐缓冲液,pH 6.0,10×,抗原修复液, for immunohistochemistry
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盐酸胍溶液,6M
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海美溴铵, ≥95%