Open AccessC-Terminal HSP90 Inhibitors Block the HIF-1 Hypoxic Response by Degrading HIF-1α through the Oxygen-Dependent Degradation Pathway
Author(s) -
Nalin Kataria,
Chloe-Anne Martinez,
Bernadette Kerr,
Samantha S. Zaiter,
Monica N Morgan,
Shelli R. McAlpine,
Kristina M. Cook
Publication year - 2019
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.33594/000000152
Subject(s) - hsp90 , heat shock protein , proteasome , gene knockdown , chemistry , protein degradation , heat shock , hsp70 , hypoxia inducible factors , microbiology and biotechnology , biochemistry , biology , apoptosis , gene
Hypoxia Inducible Factor-1α (HIF-1α) is involved in cancer progression and is stabilized by the chaperone HSP90 (Heat Shock Protein 90), preventing degradation. Previously identified HSP90 inhibitors bind to the N-terminal pocket of HSP90, which blocks binding to HIF-1α and induces HIF-1α degradation. N-terminal inhibitors have failed in the clinic as single therapy treatments partially because they induce a heat shock response. SM molecules are HSP90 inhibitors that bind to the C-terminus of HSP90 and do not induce a heat shock response. The effects of these C-terminal inhibitors on HIF-1α are unreported.