Disease relevance of PNRC1

• Additionally, using a RT-PCR analysis of mRNA on six pairs of cancer/noncancer tissues, PNRC expression was found to be significantly lower in breast cancer tissue than in noncancer tissue [1].
• Northern hybridization data showed that B4-2 is not a lymphoid specific gene and is expressed in a hepatoma cell line and also weakly transcribed or absent in a variety of other cells [2].
• Reduced expression of B4-2 protein was observed in association with hepatitis B virus infection of HCC patients [3].

High impact information on PNRC1

• A novel crosstalk mechanism between nuclear receptor-mediated and growth factor/Ras-mediated pathways through PNRC-Grb2 interaction [1].
• It has been demonstrated that proline-rich nuclear receptor coregulatory protein (PNRC) is a nuclear receptor coactivator that interacts with nuclear receptors through an SH3-binding motif located in its C-terminus [1].
• Furthermore, it was discovered that HeLa cells overexpressing PNRC grew more slowly when compared to matched controls [1].
• Coimmunoprecipitation experiment using Hela cells that express PNRC and ER was performed to confirm the interaction of PNRC and nuclear receptors in vivo in a ligand-dependent manner [4].
• Results from the mutagenesis study demonstrated that the two conserved proline (P) residues in this motif are crucial for PNRC to interact with the nuclear receptors [4].

Biological context of PNRC1

• PNRC was found to interact with both AF1 and LBD of ERalpha, and to function as a coactivator for both AF1 and AF2 transactivation functions [5].
• Differentiation was disturbed to different degrees as revealed by histology and by the expression patterns of differentiation markers keratin 10 and small proline rich protein 2 [6].
• The kinetics of transferrin acidification was found to be biphasic, indicative of fast and slow recycling pathways via early endosomes (pH 6.0) and PNRC (pH 5.6), respectively [7].

Anatomical context of PNRC1

• A polyclonal antiserum raised against recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes [2].
• A cDNA clone, B4-2, was isolated from a natural killer (NK) minus T cell subtractive library [2].
• The V-ATPase inhibitor bafilomycin selectively inhibited the transport of marker destined for lysosomal degradation in early endosomes, whereas the transport of transferrin to the perinuclear recycling compartment (PNRC) still occurred [7].
• Furthermore, the disruption of microtubules by nocodazole blocked the transport of transferrin to the PNRC in early endosomes and of lysosome-directed marker into endosomal carrier vesicles [7].

Physical interactions of PNRC1

• The molecular basis of the interaction between the proline-rich SH3-binding motif of PNRC and estrogen receptor alpha [5].

Other interactions of PNRC1

• PNRC is unique in that it has a molecular mass of 35 kDa, significantly smaller than most of the coregulatory proteins reported so far, and it is proline-rich [4].
• Our results reveal that PNRC2 has a structure and function similar to PNRC, a previously characterized coactivator [8].
• These cells did not express the differentiation markers keratin 10 and small proline rich protein 2, but did actively replicate DNA [6].

Analytical, diagnostic and therapeutic context of PNRC1

• By examining a series of deletion mutants of PNRC using the yeast two-hybrid assay, a 23-amino acid (aa) sequence in the carboxy-terminal region, aa 278-300, was shown to be critical and sufficient for the interaction with nuclear receptors [4].

References