SCREEN FOR 2-OXOGLUTARATE DEPENDENT DIOXYGENASES INVOLVED IN GROWTH CONTROL

M. KATZ; SIMMONETA S; WAPPNER P

Santa Cruz

Congreso; 5th International Meeting of the Latin American Society of Developmental Biology.; 2010

LASDB

In mammals, HIFα is posttranslationally modified by a set of prolyl hydroxylases and thereby degradated at the proteosome. During hypoxia hydroxylation is suppressed, allowing HIF to activate the transcriptional response to hypoxia. In Drosophila, Sima is hydroxylated by a single prolyl hydroxylase called Fatiga. Fatiga is a member of the Fe(II) and 2-oxoglutarate (2-OG) dependent oxygenase superfamily and utilises 2-OG as co-substrate for Sima hydroxylation. Although proline hydroxylation of HIF represents an important mode of regulation, little is known about hydroxylation of other substrates. Emerging evidence suggests that HIF is an important regulator of growth and that 2-OG may be limiting for HIF hydroxylase activity under certain conditions. Hence, regulation of 2-OG levels may be important in the control of HIF hydroxylases activity. A related possibility is that other members of the 2-OG oxygenase superfamily act as hypoxia or metabolic sensors. The aim of this work is to test whether 2-OG dependent oxygenases in addition to their function in oxygen sensing can act as growth regulator. We have performed bioinformatics predictions that suggest that more than 50 2-OG oxygenases occur in the Drosophila genome. We have utilized genetic tools available in Drosophila to analyze the different known or predicted oxygenases as possible regulators of fly growth. Using the fly wing as a model to test effects on growth, we are currently performing an RNAi-based screen against the Drosophila dioxygenases. The results of the present screen will reveal a novel group of proteins that regulates growth.