the putative rna helicase helz promotes cell proliferation, translation initiation and ribosomal protein s6 phosphorylation假定的rna解旋酶helz促进细胞增殖,翻译起始和核糖体蛋白s6磷酸化.pdfVIP

The Putative RNA Helicase HELZ Promotes Cell Proliferation, Translation Initiation and Ribosomal Protein S6 Phosphorylation 1¤ 1 2 2 1 Philippe A. Hasgall , David Hoogewijs , Marius B. Faza , Vikram G. Panse , Roland H. Wenger *, Gieri Camenisch1 ¨ ¨ ¨ ¨ 1 Institute of Physiology and Zurich Center for Integrative Human Physiology ZIHP, University of Zurich UZH, Zurich, Switzerland, 2 Institute of Biochemistry, ETH Zurich, ¨ Zurich, Switzerland Abstract 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