Journal article
Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis
Y Boglev, AP Badrock, AJ Trotter, Q Du, EJ Richardson, AC Parslow, SJ Markmiller, NE Hall, TA de Jong-Curtain, AY Ng, H Verkade, EA Ober, HA Field, D Shin, CH Shin, KM Hannan, RD Hannan, RB Pearson, SH Kim, KC Ess Show all
Plos Genetics | Published : 2013
Abstract
Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (ttis450), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In ttis450, the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, a..
View full abstractGrants
Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
This research was funded by the National Health and Medical Research Council of Australia through Project grant 433614 (JKH), Program grant 487922 (JKH), a Senior Research Fellowship (JKH), and a Howard Florey Centenary Fellowship (HV). Operational Infrastructure Support was provided by the Victorian Government, Australia. Additional support was from Australian Research Council grant DP0346823 (GJL); NIH grant DK060322 (DYRS); and CDMRP, Department of Defense, USA W81XWH-10-1-0854 (KCE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.