ING2, a tumor associated gene, enhances PAI-1 and HSPA1A expression with HDAC1 and mSin3A through the PHD domain and C-terminal
| Autor: | Seiichi Takenoshita, Teruhide Ishigame, Kensuke Kumamoto, Motonobu Saito, Shinichi Suzuki, Cutis C. Harris, Chiyo Ohkouchi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research inhibitor of growth 2 Protein Array Analysis Receptors Cytoplasmic and Nuclear histone deacetylase 1 Somatomammotropin SAP30 Biology medicine.disease_cause Biochemistry Histone Deacetylases Chromatin remodeling 03 medical and health sciences Matrix Metalloproteinase 13 Plasminogen Activator Inhibitor 1 Gene expression Genetics medicine Humans Point Mutation E2F1 HSP70 Heat-Shock Proteins Molecular Biology Gene Homeodomain Proteins Regulation of gene expression Mutation Tumor Suppressor Proteins Articles Molecular biology Up-Regulation Repressor Proteins Sin3 Histone Deacetylase and Corepressor Complex HEK293 Cells 030104 developmental biology Oncology heat-shock 70-KD protein 1A Matrix Metalloproteinase 2 plasminogen activator inhibitor-1 Molecular Medicine PHD Zinc Fingers Inhibitor of Growth Protein 1 Plasmids |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2017.7553 |
| Popis: | Inhibitor of growth 2 (ING2) is involved in chromatin remodeling and it has previously been suggested that ING2 may regulate gene expression. The authors previously identified matrix metalloproteinase 13 (MMP13) as a target gene of ING2 in colorectal cancer. The aim of the present study was to identify novel genes regulated by ING2 and histone deacetylase 1 (HDAC1) and to clarify the biological significance of the ING2 structure. The present study generated the point mutant constructs of ING2 and deletion constructs consisting of partial ING2 to investigate the effect on gene expression and verify the interaction with HDAC1, mSin3A and sap30. A microarray was performed to find novel ING2/HDAC1 target genes using cell co-overexpression of ING2 and HDAC1. Plasminogen activator inhibitor-1 (PAI-1) was upregulated with overexpression of ING1b and ING2. The mutation of the PHD domain at 218 significantly attenuated the MMP13 and PAI-1 expression, whereas the mutation at 224 resulted in increased expression. Furthermore, the expression levels were slightly reduced by the mutation of the C-terminal. The lack of the PHD domain and the C-terminal in ING2 resulted in a decreased ability to induce gene expression. The C-terminal with PHD domain, which lacked the N-terminal, maintained the transactive function for regulating the target genes. In addition to MMP13 and PAI-1, eight genes [heat shock protein family A member 1A (HSPA1A), MIR7-3 host gene, chorionic somatomammotropin hormone 1, growth arrest and DNA damage inducible b, dehydrogenase/reductase 2, galectin 1, myosin light chain 1, and VGF nerve growth factor inducible] were demonstrated to be associated with ING2/HDAC1. The present study demonstrated that ING2/HDAC1 regulated PAI-1 and HSPA1A expression and the PHD domain and the C-terminal of ING2, which are binding sites of HDAC1 and mSin3A, are essential regions for the regulation of gene expression. |
| Databáze: | OpenAIRE |
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