Figure 1.

Schematic comparison of O2 and prolyl 4-hydroxylase signaling in animals and protists. (A) The upper panel shows current thinking about how O2- and α-ketoglutarate (αKG)-dependent hydroxylation of 2 Pro residues of HIFα by PHD2 generates a degron recognized by E3VBCUb-ligase leading to its poly-ubiquitination and degradation in the 26S-proteasome, thereby interfering with its heterodimerization with HIFβ and induction of genes appropriate to response to low O2[1,2]. (B) The lower panel shows current thinking [11] about how the protist ortholog PhyA leads to hydroxylation and multi-step glycosylation of Pro143 (in Dictyostelium). Hydroxylation of Skp1 does not generate a degron [5], but it and glycosylation may affect interaction with F-box proteins (gray implies reduced activity; unpublished data) and consequently the poly-ubiquitination activity and proteasomal degradation of F-box proteins and/or substrates of the F-box proteins. Homology of elongin C of the E3VBCUb-ligase with Skp1 of the E3SCFUb-ligase is emphasized by the dotted purple line connecting their Ub-ligases.

Xu et al. BMC Developmental Biology 2012 12:31   doi:10.1186/1471-213X-12-31
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