| RRC ID |
1459
|
| Author |
Kawate H, Wu Y, Ohnaka K, Nawata H, Takayanagi R.
|
| Title |
Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.
|
| Journal |
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.
|
| Volume |
230(1-2)
|
| Pages |
77-86
|
| Published |
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
|
| Times Cited |
19
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126) |
