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Compound C inhibits hypoxic activation of HIF‐1 independent of AMPK
Author(s) -
Emerling Brooke M.,
Viollet Benoit,
Tormos Kathryn V.,
Chandel Navdeep S.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.038
Subject(s) - ampk , regulator , hypoxia (environmental) , chemistry , microbiology and biotechnology , repressor , transcription factor , amp activated protein kinase , hypoxia inducible factors , hypoxia inducible factor 1 , kinase , protein kinase a , biochemistry , biology , oxygen , gene , organic chemistry
The key transcription factor that regulates the cellular responses to hypoxia is hypoxia inducible factor‐1 (HIF‐1). The signaling mechanisms that regulate the hypoxic activation of HIF‐1 are not fully understood. Our objective here was to test whether AMP‐activated kinase (AMPK) was an upstream regulator of HIF‐1. Our results show that AMPK is not required for the hypoxic activation of HIF‐1. Interestingly, the AMPK inhibitor, Compound C, inhibits the hypoxic activation of HIF‐1 independent of AMPK. Furthermore, we demonstrate that Compound C functions as a repressor of HIF‐1 by inhibiting respiration and suppressing mitochondrial generated ROS.