Cellular retinoic acid-binding protein II (CRABP-II) is an intracellular lipid-binding protein that associates with retinoic acid with a subnanomolar affinity. We previously showed that CRABP-II enhances the transcriptional activity of the nuclear receptor with which it shares a common ligand, namely, the retinoic acid receptor (RAR), and we suggested that it may act by delivering retinoic acid...

PML-RAR induces a block of hematopoietic differentiation and acute promyelocytic leukemia. This block is based on its capacity to inactivate target genes by recruiting histone deacetylase (HDAC) and DNA methyltransferase activities. Here we report that MBD1, a member of a conserved family of proteins able to bind methylated DNA, cooperates with PML-RAR in transcriptional repression and cellular...

The disruption of retinoic acid receptor (RAR) activity that characterizes human acute promyelocytic leukemia (APL) is associated with a block to granulocytic differentiation indicating that RARs are critical regulators of normal myeloid differentiation. Nevertheless, how RAR activity might be regulated in the presumably homogenous concentration of retinoids in blood and bone marrow and how the...

Retinoic acid (RA) induces granulocytic differentiation of acute promyelocytic leukemia (APL) cells and is a useful therapeutic agent for patients with this disease. In the HL-60 promyelocytic leukemia cell line, this RA-induced granulocytic differentiation appears to be directly mediated through the RA receptor (RAR-alpha). We have previously identified a mutant subclone of HL-60 (designated H...

In mouse embryonic cells, ligand-activated retinoic acid receptors (RARs) play a key role in inhibiting pluripotency-maintaining genes and activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regulation, we performed joint RAR/RXR ChIP-seq and mRNA-seq time series during the first 48 h of the RA-induced Primitive Endoderm (PrE) differentiation ...

Adsorption desorption processes of Pb at contaminated levels in two variable charge soils were investigated. The red soil (RAR) developed on the Arenaceous rock (clayey, mixed siliceous thermic typic Dystrochrept) adsorbed more Pb2+ than the red soil (REQ) derived from the Quaternary red earths (clayey, kaolinitic thermic plinthite Aquult). The maximum adsorption values (Xm) that were obtained ...

BACKGROUND: Retinoic acid receptors (RARs) are ligand-regulated transcription factors controlling cellular proliferation and differentiation. Receptor-interacting proteins such as corepressors and coactivators play a crucial role in specifying the overall transcriptional activity of the receptor in response to ligand treatment. Little is known however on how receptor activity is controlled by i...

Retinoic acid causes a range of embryonic defects, including craniofacial abnormalities, in both birds and mammals and is believed to have a number of roles in normal development. We have previously shown that the distribution of retinoic acid receptor-beta (RAR-beta) transcripts is spatially restricted within the neural-crest-derived upper beak primordia of the chick embryo. We have now used i...

Human sirtuin 1 (SIRT1) is a NAD(+)-dependent deacetylase that participates in cell death/survival, senescence and metabolism. Although its substrates are well characterized, no direct regulators have been defined. Here, we show that SIRT1 associates with SKI-interacting protein (SKIP) and modulates its activity as a coactivator of retinoic acid receptor (RAR). Binding assays indicated that SKI...

We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G. G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action of ATRA metabolites and isomers, we assessed their binding to retinoic acid rec...