Literature DB >> 28110998

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

Verline Justilien1, Syed A Ali1, Lee Jamieson1, Ning Yin1, Adrienne D Cox2, Channing J Der2, Nicole R Murray1, Alan P Fields3.   

Abstract

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 Cι (PKCι)-mediated Ect2 phosphorylation stimulates Ect2-dependent rDNA transcription. Thus, Ect2 regulates rRNA synthesis through a PKCι-Ect2-Rac1-NPM signaling axis that is required for lung tumorigenesis.
Copyright © 2017 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Ect2; nucleophosmin, NPM; protein kinase Cι, PKCι; rRNA synthesis; tumor initiation; upstream binding factor 1, UBF1

Mesh：

Substances：

Year:  2017        PMID： 28110998      PMCID： PMC5310966          DOI： 10.1016/j.ccell.2016.12.010

Source DB:  PubMed          Journal:  Cancer Cell        ISSN： 1535-6108            Impact factor:   31.743


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