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Nat Rev Cancer. 2013 Dec;13(12):827-41. doi: 10.1038/nrc3621.

bHLH-PAS proteins in cancer.

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School of Molecular and Biomedical Science (Biochemistry) and the Centre for Molecular Pathology, University of Adelaide, South Australia 5005, Australia.


Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcription factors that sense and respond to environmental signals (such as pollutants) or to physiological signals (for example, hypoxia and circadian rhythms) through their two PAS domains. PAS domains form a generic three-dimensional fold, which commonly contains an internal cavity capable of small-molecule binding and outer surfaces adept at protein-protein interactions. These proteins are important in several pro-tumour and antitumour pathways and their activities can be modulated by both natural metabolites and oncometabolites. Recently determined structures and successful small-molecule screening programmes are now providing new opportunities to discover selective agonists and antagonists directed against this multitasking family of transcription factors.

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