We identify the RARalpha, RXRalpha and CRABPII domains required for the physical interaction of these proteins. On RARalpha and RXRalpha, the sequences correspond to the DEF and DE domains, respectively, but the interaction with CRABPII does not require the AF-2AD 'core'. On CRABPII, two interacting domains are identified (NRID1 and NRID2), one of which contains the only enhancement transactivation domain of CRABPII. The interaction is ligand-independent and does not require the ligand-binding domain of CRABPII. These results further stress that interaction of CRABPII with the nuclear receptors defines a novel level of transcriptional control.
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http://dx.doi.org/10.1016/s0014-5793(01)02938-6 | DOI Listing |
FEBS Lett
October 2024
Medical Sciences Division, Northern Ontario School of Medicine, Sudbury, Canada.
Retinoic acid is crucial for vertebrate embryogenesis, influencing anterior-posterior patterning and organogenesis through its interaction with nuclear hormone receptors comprising heterodimers of retinoic acid receptors (RARα, β, or γ) and retinoid X receptors (RXRα, β, or γ). Tissue retinoic acid levels are tightly regulated since both its excess and deficiency are deleterious. Dehydrogenase/reductase 3 (DHRS3) plays a critical role in this regulation by converting retinaldehyde to retinol, preventing excessive retinoic acid formation.
View Article and Find Full Text PDFFront Oncol
September 2024
Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
Cancer Sci
November 2024
Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Patients with BRAF-mutated colorectal cancer (BRAF CRC) are currently treated with a combination of BRAF inhibitor and anti-EGFR antibody with or without MEK inhibitor. A fundamental problem in treating patients with BRAF CRC is intrinsic and/or acquired resistance to this combination therapy. By screening 78 compounds, we identified tretinoin, a retinoid, as a compound that synergistically enhances the antiproliferative effect of a combination of BRAF inhibition and MEK inhibition with or without EGFR inhibition on BRAF CRC cells.
View Article and Find Full Text PDFEur J Med Chem
November 2024
School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, 361102, Fujian, China. Electronic address:
Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα's tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL.
View Article and Find Full Text PDFPLoS One
May 2024
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
Cofactors interacting with PPARγ can regulate adipogenesis and adipocyte metabolism by modulating the transcriptional activity and selectivity of PPARγ signaling. ZFP407 was previously demonstrated to regulate PPARγ target genes such as GLUT4, and its overexpression improved glucose homeostasis in mice. Here, using a series of molecular assays, including protein-interaction studies, mutagenesis, and ChIP-seq, ZFP407 was found to interact with the PPARγ/RXRα protein complex in the nucleus of adipocytes.
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