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Publication : Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma.

First Author  Justilien V Year  2017
Journal  Cancer Cell Volume  31
Issue  2 Pages  256-269
PubMed ID  28110998 Mgi Jnum  J:239370
Mgi Id  MGI:5828661 Doi  10.1016/j.ccell.2016.12.010
Citation  Justilien V, et al. (2017) Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma. Cancer Cell 31(2):256-269
abstractText  The guanine nucleotide exchange factor (GEF) epithelial cell transforming sequence 2 (Ect2) has been implicated in cancer. However, it is not clear how Ect2 causes transformation and whether Ect2 is necessary for tumorigenesis in vivo. Here, we demonstrate that nuclear Ect2 GEF activity is required for Kras-Trp53 lung tumorigenesis in vivo and that Ect2-mediated transformation requires Ect2-dependent rDNA transcription. Ect2 activates rRNA synthesis by binding the nucleolar transcription factor upstream binding factor 1 (UBF1) on rDNA promoters and recruiting Rac1 and its downstream effector nucleophosmin (NPM) to rDNA. Protein kinase Ciota (PKCiota)-mediated Ect2 phosphorylation stimulates Ect2-dependent rDNA transcription. Thus, Ect2 regulates rRNA synthesis through a PKCiota-Ect2-Rac1-NPM signaling axis that is required for lung tumorigenesis.
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