It appears that your browser has JavaScript disabled.

This Website requires your browser to be JavaScript enabled.

Please enable JavaScript and reload this page.

[pnr]

3 Results Advanced Search

Products (0)

Documents (3)

Site Content (0)

Can't Find What You're Looking For?

Contact Customer Service

Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation.
Since inactivation of tumor suppressor p53 functions is one of the most common features of human cancer cells, restoring p53 expression and activity is an important focus in cancer therapy. Here we report identification of photoreceptor-specific nuclear receptor (PNR)/NR2E3 as a positive regulator of p53 in a high-throughput genetic screen. In HeLa cells, PNR stimulated p53-responsive promoters in a p53-dependent fashion and induced apoptosis in several cell types. PNR also increased p53 protein stability and specific activity as a transcriptional activator. Our studies of the underlying mechanisms showed that PNR forms complexes with p53 and the acetyltransferase p300, stimulates p53 acetylation, and increases the expression of a subset of p53 target genes. Furthermore, PNR significantly boosted actinomycin D-stimulated p53 acetylation. The unique mechanisms by which PNR stimulates p53 acetylation and functions define this orphan nuclear receptor as a potentially valuable target and tool in p53-associated cancer therapy and offer new insights into the roles of PNR mutation in retinal diseases.
Document Type:

Reference

Product Catalog Number:

Multiple
Product Catalog Name:

Multiple
Dissecting the cell to nucleus, perinucleus and cytosol.
Cells have been described under the microscope as organelles containing cytoplasm and the nucleus. However, an unnoted structure exists between the cytoplasm and the nucleoplasm of eukaryotic cells. In addition to the nuclear envelope, there exists a perinuclear region (PNR or perinucleus) with unknown composition and function. Until now, an investigation of the role of the perinucleus has been restricted by the absence of a PNR isolation method. This manuscript describes a perinucleus isolation technique on the basis of its unique compact organization. The perinucleus was found to contain approximately 15 to 18% of the total proteins of the mammalian cell, almost half of the proteins of nuclei. Using four different normal and cancer cell lines, it was shown that the composition of PNR is highly dynamic. Application of the method showed that translocation of the p53 tumor-suppressor protein to the perinucleus in immortalized MEF cells is correlated with the translocation of p53-stabilizing protein, nucleophosmin (B23), to the PNR. Herein, the concept of the perinuclear region is advanced as a formal, identifiable structure. The roles of the perinucleus in maintaining genome integrity, regulation of gene expression and understanding of malignant transformation are discussed.
Document Type:

Reference

Product Catalog Number:

05-728
A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors.
Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily. Two copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand-binding domains from different NR subtypes were observed. We show that RID1 and RID2 are required for BCL11A-mediated repression of endogenous γ-globin gene and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding sites within the Bgl3 locus. In addition to their importance for BCL11A function, we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding pattern in contrast to other cofactors. In summary, our results provide new insights into the selectivity of NR/cofactor complex formation.
Document Type:

Reference

Product Catalog Number:

06-719
Product Catalog Name:

Anti-LexA Antibody, DNA-binding region