Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization [electronic resource].
- Published:
- Bethesda, Md. : National Institutes of Health (U.S.), 2015.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy - Physical Description:
- pages 7,707-7,721 : digital, PDF file
- Additional Creators:
- Argonne National Laboratory
National Institutes of Health (U.S.)
United States. Department of Energy. Office of Science
United States. Department of Energy. Office of Scientific and Technical Information - Access Online:
- www.osti.gov
- Summary:
- The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor, we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.
- Subject(s):
- Note:
- Published through SciTech Connect.
01/27/2015.
Journal of Biological Chemistry 290 12 ISSN 0021-9258 AM
Yirui Guo; Thomas H. Scheuermann; Carrie L. Partch; Diana R. Tomchick; Kevin H. Gardner. - Funding Information:
- AC02-06CH11357
R01 GM081875
P01 CA095471
F32 CA130441
RP100846
RP130513
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