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
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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