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S ‐nitrosation of Cys‐800 of HIF‐1α protein activates its interaction with p300 and stimulates its transcriptional activity
Author(s) -
Yasinska Inna M,
Sumbayev Vadim V
Publication year - 2003
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/s0014-5793(03)00807-x
Subject(s) - transactivation , nitrosation , chemistry , activator (genetics) , nitric oxide , regulator , microbiology and biotechnology , hypoxia inducible factor 1 , biochemistry , transcriptional regulation , transcription factor , biology , receptor , gene , organic chemistry
Hypoxia inducible factor 1 (HIF‐1) is a heterodimeric transcriptional complex that plays pivotal role in the regulation of cellular utilization of oxygen as well as glucose and is an essential regulator of angiogenesis in solid tumor and ischemic disorders. Recently HIF‐1α, a subunit of HIF‐1 complex, was characterized as a potential target for S ‐nitrosation, providing no information about the impact of this posttranslational modification on the protein transactivation. Cys‐800 of HIF‐1α protein has reactive SH‐group, which is critical for the recruitment of p300 co‐activator that is necessary for transcriptional activity of HIF‐1 complex. Here we report that S ‐nitrosation of Cys‐800 activates HIF‐1α–p300 interaction and stimulates protein transactivation. We have found that S ‐nitrosation of the HIF‐1α C‐terminal domain by nitric oxide derived from donors and nitric oxide synthase increases protein transcriptional activity. The increase of HIF‐1 transcriptional activity was not observed in the case of Cys‐800 substitution to Ala, though other protein thiol groups were nitrosated. Experiments with GST pull‐down assay suggest that S ‐nitrosation of Cys‐800 stimulates the recruitment of p300 co‐activator protein to the HIF‐1α C‐terminal domain.