Journalartikel

Jahr der Veröffentlichung: 2010

Seiten: 345-356

Zeitschrift: Journal of Molecular Cell Biology

Bandnummer: 2

Heftnummer: 6

ISSN: 1674-2788

eISSN: 1759-4685

Open Access Status: Bronze

DOI Link: https://doi.org/10.1093/jmcb/mjq032

Verlag: Oxford University Press

Abstract: 
T-cell intracellular antigen (TIA)-1 and TIA-1-related protein (TIAR) are mRNA-binding proteins that can aggregate within granules under specific stress conditions. In this study, we analyzed TIAR/TIA-1 aggregation under different hypoxic conditions, and studied the effects on the hypoxia-inducible factor (HIF)-1 alpha in different cancer cell lines. Under acute and pronounced hypoxic conditions TIAR/TIA-1 co-aggregated to granules and positive co-staining with eIF3 eta marker suggested these to represent stress granules. In parallel, HIF-1 alpha expression was blocked in cells displaying TIAR/TIA-1 granules. Silencing of TIAR and TIA-1 caused upregulation of HIF-1 alpha expression, as demonstrated by western blot, immunocytochemistry and HIF-1-dependent reporter gene expression. Additionally, a critical region of the 3' end of the untranslated HIF-1 alpha mRNA with possible adenosine-uridine-rich elements (AREs) was coupled to the luciferase reporter gene, causing downregulation of expression. Employing this reporter construct, inhibition of TIAR by siRNA attenuated the inhibitory cis-effect of this ARE-sequence. Furthermore, immunohistochemical analysis of A549 cell tumor xenografts revealed a nearly complementary expression of HIF-1 alpha and TIAR reflecting the control of HIF-1 alpha expression by TIAR as revealed in the cell culture studies. In sum, rapid and severe hypoxia caused co-aggregation of TIAR/ TIA-1 and these proteins suppressed HIF-1 alpha expression.

Harvard-Zitierstil: Gottschald, O., Malec, V., Krasteva, G., Hasan, D., Kamlah, F., Herold, S., et al. (2010) TIAR and TIA-1 mRNA-Binding Proteins Co-aggregate under Conditions of Rapid Oxygen Decline and Extreme Hypoxia and Suppress the HIF-1α Pathway, Journal of Molecular Cell Biology, 2(6), pp. 345-356. https://doi.org/10.1093/jmcb/mjq032

APA-Zitierstil: Gottschald, O., Malec, V., Krasteva, G., Hasan, D., Kamlah, F., Herold, S., Rose, F., Seeger, W., & Haenze, J. (2010). TIAR and TIA-1 mRNA-Binding Proteins Co-aggregate under Conditions of Rapid Oxygen Decline and Extreme Hypoxia and Suppress the HIF-1α Pathway. Journal of Molecular Cell Biology. 2(6), 345-356. https://doi.org/10.1093/jmcb/mjq032