RRC ID 1459
著者 Kawate H, Wu Y, Ohnaka K, Nawata H, Takayanagi R.
タイトル Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.
ジャーナル Mol Cell Endocrinol
Abstract Although sex steroid hormones have significant effects on bone metabolism, the molecular mechanisms of these actions have not been fully elucidated yet. We examined the functional relationship between steroid hormone receptors and Tob, a member of an anti-proliferative protein family and a negative regulator of osteoblast proliferation and differentiation. Luciferase assay using promoters carrying hormone-responsive elements revealed that both Tob1 and Tob2 proteins but not PC3 suppressed steroid hormone receptor-dependent transcriptional activation in MC3T3-E1 osteoblastic cells. Mutated Tob proteins carrying amino acid substitutions at an LXXLL motif also showed the same degree of inhibition of the transcriptional activation as the wild type. By observation of androgen receptor (AR)-tagged with green fluorescent protein under a confocal laser scanning microscope, we found that Tob1 inhibits the nuclear foci formation of dihydrotestosterone-bound AR. These results indicate that Tob family proteins may negatively regulate sex steroid hormone action in bone formation.
巻・号 230(1-2)
ページ 77-86
公開日 2005-1-31
DOI 10.1016/j.mce.2004.10.009
PII S0303-7207(04)00398-3
PMID 15664454
MeSH Amino Acid Motifs Androgen Receptor Antagonists* Animals Cell Cycle Proteins / analysis Cell Cycle Proteins / genetics Cell Cycle Proteins / physiology* Cell Nucleus / chemistry Chlorocebus aethiops Estrogen Receptor alpha / analysis Estrogen Receptor alpha / antagonists & inhibitors* Estrogen Receptor alpha / genetics Genes, Reporter / genetics Humans Immunoprecipitation Intracellular Signaling Peptides and Proteins / analysis Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / physiology* Luciferases / analysis Luciferases / genetics Mice Mutation / genetics Osteoblasts / chemistry Osteoblasts / metabolism* Receptors, Androgen / analysis Receptors, Androgen / genetics Response Elements / genetics Response Elements / physiology Transcriptional Activation / physiology* Tumor Suppressor Proteins / analysis Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / physiology*
IF 3.871
引用数 19
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)