The estrogen-responsive B box protein is a novel regulator of the retinoid signal

The Journal of Biological Chemistry
Belamy B CheungG M Marshall

Abstract

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 togethe...Continue Reading

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Citations

Feb 14, 2013·Apoptosis : an International Journal on Programmed Cell Death·Patrick Y KimBelamy B Cheung
Aug 26, 2011·Nature Reviews. Immunology·Caroline JefferiesRowan Higgs
Mar 5, 2010·Molecular Medicine·Daniela SpanoAchille Iolascon
Jul 20, 2007·Differentiation; Research in Biological Diversity·Nigel P Mongan, Lorraine J Gudas
Feb 6, 2007·Fertility and Sterility·William H Catherino, Minnie Malik
Dec 11, 2019·Bioscience Reports·Yonghu XuGuofeng Xu
Jan 4, 2022·Journal of Gastrointestinal Cancer·Mina Seifi InallouMehdi Haghi

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