The estrogen-responsive B box protein is a novel regulator of the retinoid signal
Autor: | Belamy B. Cheung, Michelle Lee, Murray D. Norris, Joanne Yan, Deborah A. Zajchowski, Glenn M. Marshall, Andrew Bohlken, Jessica L. Bell, Maria Kavallaris, Michelle Haber, Wayne Thomas, Hsiao-Lai Liu, Ben Roediger, Anna Raif, Anne Poljak, Stewart A. Smith |
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Rok vydání: | 2006 |
Předmět: |
Small interfering RNA
Lung Neoplasms Transcription Genetic medicine.drug_class Receptors Retinoic Acid Ubiquitin-Protein Ligases Response element Molecular Sequence Data Retinoic acid Antineoplastic Agents Breast Neoplasms Tretinoin Biology Promyelocytic Leukemia Protein Biochemistry Tripartite Motif Proteins Promyelocytic leukemia protein chemistry.chemical_compound Neuroblastoma Transcription (biology) Cell Line Tumor medicine Humans Amino Acid Sequence RNA Small Interfering Molecular Biology Tumor Suppressor Proteins Histone deacetylase inhibitor Nuclear Proteins Cell Biology Neoplasm Proteins Protein Structure Tertiary DNA-Binding Proteins Gene Expression Regulation Neoplastic Retinoic acid receptor chemistry Cancer cell biology.protein Cancer research Cell Division Signal Transduction Transcription Factors |
Zdroj: | The Journal of biological chemistry. 281(26) |
ISSN: | 0021-9258 |
Popis: | Retinoic acid (RA) induces growth arrest, cell death, and differentiation in many human cancer cells in vitro and has entered routine clinical use for the treatment of several human cancer types. One mechanism by which cancer cells evade retinoid-induced effects is through repression of retinoic acid receptor beta (RARbeta) gene transcription. The RA response element beta (betaRARE) is the essential DNA sequence required for retinoid-induced RARbeta transcription. Here we show that the estrogen-responsive B box protein (EBBP), a member of the RING-B box-coiled-coil protein family, is a betaRARE-binding protein. EBBP undergoes serine threonine phosphorylation and enhanced protein stability after RA treatment. Following RA treatment, we also observed increased nuclear EBBP levels in aggregates with the promyelocytic leukemia protein at promyelocytic leukemia nuclear bodies. EBBP enhanced RA-responsive RARbeta transcription in RA-sensitive and -resistant cancer cells, which were resistant to both a histone deacetylase inhibitor and a demethylating agent. EBBP-specific small interfering RNA reduced basal and RA-induced RARbeta expression. EBBP increased betaRARE-transactivating function through its coiled-coil domain. Taken together, our work suggests that EBBP may have a pivotal role in the retinoid anti-cancer signal. |
Databáze: | OpenAIRE |
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