RESUMO
Hypoxia-inducible factor-1 (HIF-1) has a central role in the mammalian program by which cells respond to hypoxia in both physiological and pathological situations. HIF-1 transcriptional activity, protein stabilization, protein-protein interaction, and cellular localization are mainly modulated by Post-translational modifications such as hydroxylation, acetylation, phosphorylation, S-nitrosylation, and SUMOylation. Here, we summarize current knowledge about Post-translational HIF-1 regulation and give additional information about useful methods to determine some of these various modifications.
Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Acetilação , Sequência de Aminoácidos , Animais , Linhagem Celular , Escherichia coli/genética , Humanos , Hidroxilação , Fator 1 Induzível por Hipóxia/biossíntese , Fator 1 Induzível por Hipóxia/isolamento & purificação , Imunoprecipitação , Dados de Sequência Molecular , Fosforilação , Biossíntese de Proteínas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismoRESUMO
Hypoxia is an important physiological condition during embryonic development. Hypoxia-inducible factor (HIF) is the mediator of hypoxic response of cells. The prolyl hydroxylase (PHD) of HIF plays a key role in stabilizing of HIF and the oxygen homeostasis of organisms. In this study, we isolated two PHD proteins, PHD45 and PHD28, and characterized them during the embryonic development of Xenopus laevis, which is an excellent model for embryonic development because of the ease of embryonic manipulation and the feasibility of transgenesis. Based on amino acid sequences, Xenopus PHD45 and PHD28 were homologous with human PHD2 and PHD3, respectively. In embryonic development, PHD45 expression was complementary to that of PHD28. xHIF-1alpha protein level was at a maximum around stage 20 when expression of PHD45 disappeared, while expression of PHD28 reached a maximum at stage 20, suggesting that PHD28 is inducible by HIF-1alpha. Recently, Siah2 was found to be an ubiquitin ligase of PHD proteins and to regulate degradation of PHD proteins. Over-expression of xSiah2 decreased PHD45 but not PHD28 and caused the small-eye phenotype of Xenopus. Additional over-expression of PHD47 rescued the abnormality caused by xSiah2, suggesting that the level of expression or activity of PHD proteins is important to the maintenance of homeostasis in embryonic development.
