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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48709

Hasgall, P A; Hoogewijs, D; Faza, M B; Panse, V G; Wenger, R H; Camenisch, G (2011). The putative RNA helicase HELZ promotes cell proliferation, translation initiation and ribosomal protein S6 phosphorylation. PLoS ONE, 6(7):e22107.

Published Version


The hypoxia–inducible transcription factor (HIF) is a key component of the cellular adaptation mechanisms to hypoxic
conditions. HIFa subunits are degraded by prolyl-4-hydroxylase domain (PHD) enzyme-dependent prolyl-4-hydroxylation of
LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFa proteins contain
two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ
proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is
not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA
helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to
demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ
suppression had the opposite effect. Although HELZ interacted with the poly(A)-binding protein (PABP) via its PAM2 motif,
PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational
initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of
ribosomal protein S6.

Contributors:Institute of Biochemistry, ETH Zürich
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Deposited On:19 Jul 2011 07:45
Last Modified:27 Nov 2013 22:33
Publisher:Public Library of Science
Funders:Swiss National Science Foundation, Marie Curie Intra-European Fellowship, ETH Zürich, European Research Council
Publisher DOI:10.1371/journal.pone.0022107
PubMed ID:21765940
Citations:Web of Science®. Times Cited: 3
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Scopus®. Citation Count: 3

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