title: p150/glued modifies nuclear estrogen receptor function.
abstract: Estrogen modulates gene expression through interactions with estrogen receptors (ERs) that bind chromosomal target genes. Recent studies have suggested an interaction between the cytoskeletal system and estrogen signaling; these have implicated a role of cytoplasmic microtubules in scaffolding ERalpha and enhancing nongenomic function; in addition, other experiments demonstrate that dynein light chain 1 may chaperone ERalpha to the nucleus, indirectly increasing transcriptional potency. Actin/myosin and dynein light chain 1 are also required for estrogen-mediated chromosomal movement that is required for transcriptional up-regulation of ERalpha targets. We present evidence that the dynactin component, p150/glued, directly influences the potency of nuclear ER function. Increasing the stoichiometric ratio of p150/glued and ERalpha by overexpression enhances estrogen responses. ERalpha enhancement by p150/glued does not appear to be influenced by shifts in subcellular localization because microtubule disruption fails to increase nuclear ERalpha. Rather, we find that modest amounts of p150/glued reside in the nucleus of cells, suggesting that it plays a direct role in nuclear transcription. Notably, p150/glued is recruited to the pS2 promoter in the presence of hormone, and, in MCF-7 cells, knockdown of p150/glued levels reduces estrogen-dependent transcription. Our results suggest that p150/glued modulates estrogen sensitivity in cells through nuclear mechanisms.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109-5622, USA.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Christina
authors.initials: C
authors.lastname: Chae
authors.forename: Michael M
authors.initials: MM
authors.lastname: Wang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D000072159:Dynactin Complex; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008869:Microtubule-Associated Proteins