Molecular mechanism of CCAAT-enhancer binding protein recruitment by the TRIB1 pseudokinase
- Author(s)
- Murphy, JM; Nakatani, Y; Jamieson, SA; Dai, W; Lucet, IS; Mace, PD;
- Details
- Publication Year 2015-11-03,Volume 23,Issue #11,Page 2111-2121
- Journal Title
- Structure
- Publication Type
- Journal Article
- Abstract
- CCAAT-enhancer binding proteins (C/EBPs) are transcription factors that play a central role in the differentiation of myeloid cells and adipocytes. Tribbles pseudokinases govern levels of C/EBPs by recruiting them to the COP1 ubiquitin ligase for ubiquitination. Here, we present the first crystal structure of a Tribbles protein, which reveals a catalytically inactive TRIB1 pseudokinase domain with a unique adaptation in the alphaC helix. A second crystal structure and biophysical studies of TRIB1 with its C-terminal extension, which includes the COP1-binding motif, show that the C-terminal extension is sequestered at a site formed by the modified TRIB1 alphaC helix. In addition, we have identified and characterized the TRIB1 substrate-recognition sequence within C/EBPalpha, which is evolutionarily conserved in C/EBP transcription factors. Binding studies indicate that C/EBPalpha recruitment is weaker in the presence of the C-terminal COP1-binding motif, but the magnitude of this effect suggests that the two bind distinct rather directly overlapping binding sites.
- Publisher
- Cell Press
- Research Division(s)
- Cell Signalling And Cell Death; Chemical Biology
- PubMed ID
- 26455797
- Publisher's Version
- https://doi.org/10.1016/j.str.2015.08.017
- Open Access at Publisher's Site
https://doi.org/10.1016/j.str.2015.08.017- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-10-28 03:33:33
Last Modified: 2018-02-16 09:03:43