Premium
Signalling hypoxia by protein hydroxylation: Transcriptional architecture of the HIF response
Author(s) -
Ratcliffe Peter J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.100.1
Subject(s) - hydroxylation , transcription factor , hypoxia inducible factor 1 , microbiology and biotechnology , hypoxia (environmental) , transcription (linguistics) , signal transduction , biology , transcriptional regulation , hedgehog signaling pathway , hypoxia inducible factors , biochemistry , chemistry , computational biology , gene , enzyme , oxygen , organic chemistry , linguistics , philosophy
Animal use a set of 2‐oxoglutarate dependent dioxygenases to signal cellular oxygen levels to the transcription factor, HIF, via the post‐translational hydroxylation of specific prolyl and asparaginyl residues. These hydroxylations promote the inactivation and proteolytic destruction of HIF and hence regulate a broad range of cellular and systemic responses to hypoxia. The involvement of this system in a many medically important physiological responses presents both an opportunity and challenge, particularly in defining how the system operates to generate co‐ordinated physiological responses, and in understanding how it might be manipulated therapeutically in specific medical conditions. Advances in the understanding of the pan‐genomic architecture of the HIF transcriptional response, will be described together with the implications of activating such extensive pathways in cancer, and mechanisms that modulate the oncogenic output of HIF pathway activation.