Requirement of the Co-repressor Homeodomain-interacting Protein Kinase 2 for Ski-mediated Inhibition of Bone Morphogenetic Protein-induced Transcriptional Activation
| Autor: | Shunsuke Ishii, Matiullah Khan, Chie Kanei-Ishii, Jun Harada, Kenji Kokura, Teruaki Nomura, Yongsok Kim |
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| Rok vydání: | 2003 |
| Předmět: |
Transcription
Genetic Amino Acid Motifs Smad Proteins SMAD Mitogen-activated protein kinase kinase Proto-Oncogene Mas Biochemistry Adenosine Triphosphate ASK1 Phosphorylation Luciferases Promoter Regions Genetic Genes Dominant Glutathione Transferase biology DNA-Binding Proteins Bone Morphogenetic Proteins embryonic structures Cell Division Plasmids Protein Binding Signal Transduction Transcriptional Activation animal structures Recombinant Fusion Proteins Molecular Sequence Data Protein Serine-Threonine Kinases Transfection Gene Expression Regulation Enzymologic Histone Deacetylases Cell Line Smad1 Protein Proto-Oncogene Proteins Humans Amino Acid Sequence c-Raf Molecular Biology Models Genetic Sequence Homology Amino Acid MAP kinase kinase kinase Akt/PKB signaling pathway Cyclin-dependent kinase 2 Bone morphogenetic protein 10 Cell Biology Alkaline Phosphatase Precipitin Tests Molecular biology Protein Structure Tertiary Microscopy Fluorescence Trans-Activators biology.protein Carrier Proteins human activities |
| Zdroj: | Journal of Biological Chemistry. 278:38998-39005 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m307112200 |
| Popis: | Multiple co-repressors such as N-CoR/SMRT, mSin3, and the c-ski proto-oncogene product (c-Ski) mediate the transcriptional repression induced by Mad and the thyroid hormone receptor by recruiting the histone deacetylase complex. c-Ski also binds directly to Smad proteins, which are transcriptional activators in the transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) signaling pathways, and inhibits TGF-beta/BMP-induced transcriptional activation. However, it remains unknown whether other co-repressor(s) are also involved with Ski in the negative regulation of the TGF-beta/BMP signaling pathways. Here, we report that the co-repressor homeodomain-interacting protein kinase 2 (HIPK2) directly binds to both c-Ski and Smad1. HIPK2 efficiently inhibited Smad1/4-induced transcription from the Smad site-containing promoter. A dominant negative form of HIPK2, in which the ATP binding motif in the kinase domain and the putative phosphorylation sites were mutated, enhanced Smad1/4-dependent transcription and the BMP-induced expression of alkaline phosphatase. Furthermore, the c-Ski-induced inhibition of the Smad1/4-dependent transcription was suppressed by a dominant negative form of HIPK2. The HIPK2 co-repressor activity may be regulated by an uncharacterized HIPK2 kinase. These results indicate that HIPK2, together with c-Ski, plays an important role in the negative regulation of BMP-induced transcriptional activation. |
| Databáze: | OpenAIRE |
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