Diphthamide modification of eEF2 is required for gut tumor‐like hyperplasia induced by oncogenic Ras. (5th January 2020)

• Record Type: Journal Article
• Authors: Tsuda‐Sakurai, Kayoko; Kimura, Masaki; Miura, Masayuki
• Is Part Of: Genes to cells. Volume 25:Number 2(2020)
• Page Start: 76
• Page End: 85
• Publication Date: 2020-01-05
• Subjects: diphthamidation -- Drosophila -- Myc -- Ras -- translation -- tumor; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12742
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Eukaryotic elongation factor 2 (eEF2) undergoes a unique post‐translational modification called diphthamidation. Although eEF2 diphthamidation is highly conserved, its pathophysiological function is still largely unknown. To elucidate the function of diphthamidation in tumor, we examined the involvement of diphthamidation pathway enzyme Dph5 in tumor progression in Drosophila adult gut. Expression of oncogenic Ras V12 in gut intestinal stem cells (ISCs) and enteroblasts (EBs) causes hypertrophy and disruption of gut epithelia, and shortened life span. Knockdown of Dph5 ameliorated these pathogenic phenotypes. Dph5 is required for gross translation activation and high dMyc protein level in Ras V12 tumor‐like hyperplasia. Transcriptome analysis revealed that Dph5 is involved in the regulation of ribosome biogenesis genes. These results suggest that diphthamidation is required for translation activation partly through the regulation of ribosome biogenesis in Ras‐induced tumor‐like hyperplasia model in Drosophila gut. Abstract : Expression of oncogenic RasV12 in gut intestinal stem cells (ISCs) and enteroblasts (EBs) causes hypertrophy and disruption of gut epithelia and shortened life span. Knockdown of Dph5 ameliorated these pathogenic phenotypes.