Cell Biology

HIF Puts on the Brakes

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Science  01 Mar 2013:
Vol. 339, Issue 6123, pp. 1012
DOI: 10.1126/science.339.6123.1012-b

The ability of most cells to respond appropriately to availability or absence of oxygen is a fundamental requirement for survival. Much of the physiological response of a cell or organism to hypoxia, from angiogenesis and metabolic changes to control of cell division, is coordinated by the transcription factor hypoxia-inducible factor-1 (HIF-1). Hubbi et al. report that the HIF-1α subunit also has a nontranscriptional role in promoting arrest of the cell division cycle when cells sense hypoxia. In cells deprived of oxygen, HIF-1α accumulated and bound to the prereplication complex, a set of proteins that mark origins of DNA replication, thus rapidly blocking DNA replication and cell division. The transcriptonal transactivation domain of HIF-1α was not required for this effect. HIF-1α appears to be a balancing point for the cell's response to oxygen: Growth-promoting signals oppose the actions of HIF-1α and promote its binding to another protein at replication origins, the helicase MCM (minichromosome maintenance), which enhances degradation of HIF-1α.

Sci. Signal. 6, ra10 (2013).

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