In breast cancer cells, cytoplasmic localization of the estradiol receptor alpha (ERalpha) regulates estradiol-dependent S phase entry. We identified a nuclear export sequence (NES) in ERalpha and show that its export is dependent on both estradiol-mediated phosphatidylinositol-3-kinase (PI3K)/AKT activation and chromosome region maintenance 1 (CRM1). A Tat peptide containing the ERalpha NES disrupts ERalpha-CRM1 interaction and prevents nuclear export of ERalpha- and estradiol-induced DNA synthesis. NES-ERalpha mutants do not exit the nucleus and inhibit estradiol-induced S phase entry; ERalpha-dependent transcription is normal. ERalpha is associated with Forkhead proteins in the nucleus, and estradiol stimulates nuclear exit of both proteins. ERalpha knockdown or ERalpha NES mutations prevent ERalpha and Forkhead nuclear export. A mutant of forkhead in rhabdomyosarcoma (FKHR), which cannot be phosphorylated by estradiol-activated AKT, does not associate with ERalpha and is trapped in the nucleus, blocking S phase entry. In conclusion, estradiol-induced AKT-dependent phosphorylation of FKHR drives its association with ERalpha, thereby triggering complex export from the nucleus necessary for initiation of DNA synthesis and S phase entry.
Pubmed ID: 18644889 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentions