論文 - 詳細
| RRC ID | 39361 |
|---|---|
| 著者 | Tintut Y, Parhami F, Le V, Karsenty G, Demer LL. |
| タイトル | Inhibition of osteoblast-specific transcription factor Cbfa1 by the cAMP pathway in osteoblastic cells. Ubiquitin/proteasome-dependent regulation. |
| ジャーナル | J Biol Chem |
| Abstract |
The cAMP pathway, a major intracellular pathway mediating parathyroid hormone signal, regulates osteoblastic function. Parathyroid hormone (through activation of protein kinase A) has also been shown to stimulate ubiquitin/proteasome activity in osteoblasts. Since the osteoblast-specific transcription factor Osf2/Cbfa1 is important for differentiation of osteoblastic cells, we examined the roles of the cAMP and ubiquitin/proteasome pathways in regulation of Cbfa1. In the osteoblastic cell line, MC3T3-E1, continuous treatment with cAMP elevating agents inhibited both osteoblastic differentiation based on alkaline phosphatase assay and DNA binding ability of Cbfa1 based on a gel retardation assay. Cbfa1 inhibition was paralleled by an inhibitory effect of forskolin on Cbfa1-regulated genes. Northern and Western blot analyses suggested that the inhibition of Cbfa1 by forskolin was mainly at the protein level. Pretreatment with proteasome inhibitors prior to forskolin treatment reversed the effect of forskolin. Furthermore, addition of proteasome inhibitors to forskolin-pretreated samples resulted in recovery of Cbfa1 protein levels and accumulation of polyubiquitinated forms of Cbfa1, indicating a role for the proteasome pathway in the degradation of Cbfa1. These results suggest that suppression of osteoblastic function by the cAMP pathway is through proteolytic degradation of Cbfa1 involving a ubiquitin/proteasome-dependent mechanism. |
| 巻・号 | 274(41) |
| ページ | 28875-9 |
| 公開日 | 1999-10-8 |
| DOI | 10.1074/jbc.274.41.28875 |
| PII | S0021-9258(19)51916-0 |
| PMID | 10506130 |
| MeSH | Alkaline Phosphatase / genetics Animals Calcium / metabolism Cell Differentiation Cell Line Colforsin / pharmacology Core Binding Factor Alpha 1 Subunit Cyclic AMP / agonists Cyclic AMP / metabolism* Cysteine Endopeptidases / metabolism Cysteine Proteinase Inhibitors / pharmacology DNA-Binding Proteins / metabolism Gene Expression Regulation / drug effects Mice Multienzyme Complexes / metabolism Neoplasm Proteins* Osteoblasts / metabolism* Parathyroid Hormone / pharmacology Proteasome Endopeptidase Complex RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / antagonists & inhibitors Transcription Factors / genetics* Ubiquitins / metabolism |
| IF | 4.238 |
| 引用数 | 114 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) |