Ruas Jorge L, Poellinger Lorenz
Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden.
Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):514-22. doi: 10.1016/j.semcdb.2005.04.001.
Adaptation to conditions of limited oxygen availability (hypoxia) is a critical determinant of cell and tissue viability in several physiological and pathophysiological conditions. The hypoxia-inducible factor (HIF) is an oxygen-sensitive transcriptional activator that, under hypoxia, upregulates the expression of genes involved in the control of glucose metabolism, angiogenesis and cellular proliferation, among others. Activation of HIF to a fully competent transcriptional regulatory protein complex is a multi-step process that involves control of protein stability, subcellular localization, DNA-binding and interaction with transcriptional coregulators. The identity, regulation and hierarchy of interactions between several components of the HIF signal transduction pathway has been the object of intense study over the past decade and will be the subject of this review. Particular emphasis is given to the process of coordinated coactivator recruitment within the cell nucleus. The implications for future development of angiogenic/antiangiogenic therapeutic strategies of HIF activation/inactivation are discussed.
在多种生理和病理生理条件下，适应有限的氧气供应状况（缺氧）是细胞和组织生存能力的关键决定因素。缺氧诱导因子（HIF）是一种氧敏感的转录激活因子，在缺氧条件下，它会上调参与葡萄糖代谢、血管生成和细胞增殖等调控的基因表达。HIF激活成为一个完全有活性的转录调节蛋白复合物是一个多步骤过程，涉及蛋白质稳定性、亚细胞定位、DNA结合以及与转录共调节因子的相互作用的控制。在过去十年中，HIF信号转导途径几个组分之间相互作用的身份、调控和层次结构一直是深入研究的对象，本文将对此进行综述。特别强调细胞核内协同共激活因子募集的过程。还讨论了HIF激活/失活对血管生成/抗血管生成治疗策略未来发展的影响。
