AKT1 has dual actions on the glucocorticoid receptor by cooperating with 14-3-3

作者：Habib Tanwir; Sadoun Ameera; Nader Nancy; Suzuki Shigeru; Liu Wei; Jithesh Puthen V; Kino Tomoshige^*

来源：Molecular and Cellular Endocrinology, 2017, 439(C): 431-443.

DOI：10.1016/j.mce.2016.10.002

• Histone modification
• Nuclear translocation
• Phosphorylation
• Protein-protein interaction
• Transcriptomics

Glucocorticoids are important therapeutic compounds for acute lymphoblastic leukemia (ALL). AIM or the protein kinase B is frequently activated in ALL, and contributes to the development of glucocorticoid resistance. We examined impact of AKT1 on glucocorticoid receptor (GR)-induced transcriptional activity in cooperation with phospho-serine/threonine-binding protein 14-3-3. AKT1 has two distinct actions on GR transcriptional activity, one through segregation of GR in the cytoplasm by phosphorylating GR at Ser-134 and subsequent association of 14-3-3, and the other through direct modulation of GR transcriptional activity in the nucleus. For the latter, AKT1 and 14-3-3 are attracted to DNA -bound GR, accompanied by AKT1-dependent p300 phosphorylation, H3S10 phosphorylation and H3K14 acetylation at the DNA site. These two actions of AKT1 regulate distinct sets of glucocorticoid-responsive genes. Our results suggest that specific inhibi

• 出版日期2017-1-5
• 单位NIH