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The HIF-1 Family of bHLH-PAS Proteins: Master Regulators of Oxygen Homeostasis

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PAS Proteins: Regulators and Sensors of Development and Physiology

Abstract

Above all other elements, molecules, and compounds, O2 is the critical environmental substrate that must be delivered to all cells of metazoan organisms on a virtually continuous basis for survival. The evolution of multicellular animals in which oxygen could no longer be acquired by all cells via simple diffusion necessitated the co-evolution of physiological systems specialized for O2 delivery, which became progressively more complex as body size increased, most notably with the appearance of the vertebrates. The HIF-1 (hypoxia-inducible factor 1) family of bHLH-PAS transcription factors appears to have evolved as a specialized system for regulating oxygen homeostasis at the level of gene expression in metazoans. HIF-1 is present in simple invertebrates such as the roundworm Caenorhabditis elegans, which consists of ~103 cells and relies on simple diffusion for O2 transport, more complex invertebrates such as the fruit fly Drosophila melanogaster, in which O2 is distributed through the body via a set of specialized tracheal tubes, and in complex vertebrates such as Homo sapiens, which consist of > 1013 cells that are supplied with O2 via the combined functioning of highly complex and specialized circulatory and respiratory systems.

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  1. The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Gregg L. Semenza

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  1. The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Stephen T. Crews

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Semenza, G.L. (2003). The HIF-1 Family of bHLH-PAS Proteins: Master Regulators of Oxygen Homeostasis. In: Crews, S.T. (eds) PAS Proteins: Regulators and Sensors of Development and Physiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0515-0_8

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  • DOI: https://doi.org/10.1007/978-1-4615-0515-0_8

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