TY - JOUR
T1 - Hypoxia-Inducible Factors Per/ARNT/Sim Domains
T2 - Structure and Function
AU - Scheuermann, Thomas H.
AU - Yang, Jinsong
AU - Zhang, Lei
AU - Gardner, Kevin H.
AU - Bruick, Richard K.
PY - 2007
Y1 - 2007
N2 - Hypoxia-inducible factors (HIFs) are key transcriptional regulators of genes involved in cellular adaptation to reduced oxygen availability through effects on anaerobic metabolism, oxygen delivery, angiogenesis, and cellular survival and proliferation. As such, HIFs contribute to the pathogenesis of diseases in which oxygen availability is compromised, notably ischemia and tumorigenesis. Though tremendous progress has been made in elucidating the mechanisms underlying O2-dependent regulation of HIF by Fe(II)- and 2-oxoglutarate-dependent dioxygenases, HIF induction can be uncoupled from these modes of regulation in diseases such as cancer. Consequently, renewed interest has developed in understanding the structure/function relationships of individual Per/ARNT/Sim (PAS) domains that are important for maintaining transcriptionally active HIF complexes, regardless of the manner by which HIF is induced. This review highlights strategies for the biophysical and biochemical characterization of the PAS domains found within both HIF subunits and provides a platform for future efforts to exploit these domains in therapeutic settings.
AB - Hypoxia-inducible factors (HIFs) are key transcriptional regulators of genes involved in cellular adaptation to reduced oxygen availability through effects on anaerobic metabolism, oxygen delivery, angiogenesis, and cellular survival and proliferation. As such, HIFs contribute to the pathogenesis of diseases in which oxygen availability is compromised, notably ischemia and tumorigenesis. Though tremendous progress has been made in elucidating the mechanisms underlying O2-dependent regulation of HIF by Fe(II)- and 2-oxoglutarate-dependent dioxygenases, HIF induction can be uncoupled from these modes of regulation in diseases such as cancer. Consequently, renewed interest has developed in understanding the structure/function relationships of individual Per/ARNT/Sim (PAS) domains that are important for maintaining transcriptionally active HIF complexes, regardless of the manner by which HIF is induced. This review highlights strategies for the biophysical and biochemical characterization of the PAS domains found within both HIF subunits and provides a platform for future efforts to exploit these domains in therapeutic settings.
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U2 - 10.1016/S0076-6879(07)35001-5
DO - 10.1016/S0076-6879(07)35001-5
M3 - Article
C2 - 17998046
AN - SCOPUS:39749179024
SN - 0076-6879
VL - 435
JO - Methods in Enzymology
JF - Methods in Enzymology
ER -