PHD1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein Cep192.
Bottom Line: Importantly, PHD1 is also required for primary cilia formation.Cep192 is hydroxylated by PHD1 on proline residue 1717.This hydroxylation is required for binding of the E3 ubiquitin ligase SCF(Skp2), which ubiquitinates Cep192, targeting it for proteasomal degradation.
Affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.Show MeSH
Related in: MedlinePlus
Mentions: To determine whether PHDs have a role in cell-cycle progression, we independently depleted each of the three isoforms PHD1–3 by siRNA in HeLa Kyoto cells (Figures S1A–S1D available online). Whereas depletion of either PHD2 or PHD3 caused little or no alteration of the cell-cycle profile, depletion of PHD1 increased the G2/M population of cells and decreased the G1 population (Figure 1A). In contrast, and as previously observed (Culver et al., 2011), HIF-1α depletion led to an increase of cells in G1 (Figure 1A). Further analysis revealed that PHD1 knockdown increased the mitotic index (Figure 1B). When the endogenous PHD1 protein was removed by targeting the 3′ UTR of its mRNA with siRNA, this effect could be reversed by the expression of PHD1 from a cDNA lacking the siRNA target site (Figure 1B). These data suggest that PHD1 is required for mitotic progression.
Affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.