Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation.

Autor:	Zhang Q; College of Life Science, Northeast Forestry University, Harbin, China Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA Present address: Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI 48109, USA., Wan M; Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Shi J; College of Life Science, Northeast Forestry University, Harbin, China., Horita DA; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Miller LD; Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Kute TE; Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Kridel SJ; Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Kulik G; Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA Life Sciences Program, College of Science & General Studies, Alfaisal University, Riyadh 11533, Saudi Arabia., Sui G; College of Life Science, Northeast Forestry University, Harbin, China Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA gcsui@nefu.edu.cn gsui@wakehealth.edu.
Jazyk:	angličtina
Zdroj:	Journal of molecular cell biology [J Mol Cell Biol] 2016 Jun; Vol. 8 (3), pp. 232-43. Date of Electronic Publication: 2016 Jan 13.
DOI:	10.1093/jmcb/mjw002
Abstrakt:	Yin Yang 1 (YY1) regulates both gene expression and protein modifications, and has shown a proliferative role in cancers. In this study, we demonstrate that YY1 promotes AKT phosphorylation at S473, a marker of AKT activation. YY1 expression positively correlated with AKT(S473) phosphorylation in a tissue microarray and cultured cells of breast cancer, but negatively associated with the distant metastasis-free survival of 166 breast cancer patients. YY1 promotes AKT phosphorylation at S473 through direct interaction with AKT, and the AKT-binding site is mapped to the residues G201-S226 on YY1. These residues are also involved in YY1 interaction with Mdm2, Ezh2, and E1A, and thus are designated as the oncogene protein binding (OPB) domain. YY1-promoted AKT phosphorylation relies on the OPB domain but is independent of either transcriptional activity of YY1 or the activity of phosphoinositide-3-kinases. We also determine that YY1-promoted mTORC2 access to AKT leads to its phosphorylation at S473. Importantly, a peptide based on the OPB domain blocks YY1 interaction with AKT and reduces AKT phosphorylation and cell proliferation. Thus, we demonstrate for the first time that YY1 promotes mTORC2-mediated AKT activation and disrupting YY1-AKT interaction by OPB domain-based peptide may represent a potential strategy for cancer therapy. (© The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.)
Databáze:	MEDLINE
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