Hypoxia-inducible factor-1 (HIF-1).

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that acts as a master regulator of gene expression induced by low oxygen conditions (hypoxia) (1). Genes regulated by HIF-1 broadly include those involved in oxygen homeostasis and glucose-energy metabolism. Some genes regulated by HIF help to augment tissue oxygen supply, while others confer increased tolerance to severe oxygen deprivation (2). The protective effects induced by HIF are not immediate, since the response to HIF activation requires de novo transcription and translation of new proteins. Hence, HIF activation is an anticipatory response that begins with even mild hypoxia. HIF-1 is a heterodimer consisting of and subunits. Both proteins are constitutively expressed, but the subunit protein is rapidly degraded by the 28S proteasomal system under normoxic conditions (3). Under hypoxic conditions, degradation of HIF-1 is inhibited, allowing the protein to accumulate in the cell, heterodimerize, relocate to the nucleus, and activate transcription.

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