Alternative titles; symbols
HGNC Approved Gene Symbol: PPRC1
Cytogenetic location: 10q24.32 Genomic coordinates (GRCh38): 10:102,119,889-102,150,333 (from NCBI)
PPRC1 is a coactivator that functions through NRF1 (600879) in response to proliferative signals (Andersson and Scarpulla, 2001).
By searching cDNA libraries for sequences with the potential to encode large proteins in brain, Nagase et al. (1998) identified a partial cDNA for PPRC1, which they termed KIAA0595, encoding a predicted 1,520 amino acids. RT-PCR analysis revealed ubiquitous expression.
By database searching for sequences similar to PGC1 (PPARGC1A; 604517) followed by full-length cloning, Andersson and Scarpulla (2001) identified PRC, a 1,664-residue protein. Both PRC and PGC1 contain an N-terminal LXXLL coactivator sequence, a central proline-rich region, and a C-terminal RS domain and RNA recognition motif. Confocal microscopy demonstrated nuclear localization. Northern blot analysis revealed expression of 5- and 6-kb transcripts in all tissues, with somewhat higher expression of the smaller transcript especially in skeletal muscle and heart. Unlike PGC1, PRC is only modestly cold-regulated, and expression in brown fat is only transient. Immunoblot analysis showed expression of a 150-kD protein. RNase protection analysis indicated that PRC is cell cycle-regulated and is induced early in the G0-G1 transition. Andersson and Scarpulla (2001) showed that, like PGC1, PRC is a transcriptional coactivator through NRF1 and that the PRC activation domain interacts directly with the NRF1 DNA-binding domain. Site-directed mutagenesis demonstrated that PRC can coactivate through NRF1 in the context of a natural promoter. Andersson and Scarpulla (2001) concluded that PRC is a functional relative of PGC1 that operates through NRF1 and possibly other activators.
By exposing umbilical vein endothelial cells to lipopolysaccharide (LPS), Chengye et al. (2013) observed a downregulation of PRC expression. Overexpression of PRC inhibited, through NFKB (see 164011), the expression of endothelial cell adhesion molecules such as VCAM1 (192225) and SELE (131210), and attenuates the adhesion of a monocytic cell line to endothelial cell surfaces.
Andersson and Scarpulla (2001) determined that the PPRC1 gene contains 14 exons and spans 25 kb.
By quantifying transcripts of PRC, NRF1, and TFAM (600438), Savagner et al. (2003) observed overexpression of all 3 genes in thyroid oncocytoma compared to normal thyroid tissue, concomitantly with an increase in cytochrome oxidase activity and mitochondrial DNA content, as estimated by ND5 (MTND5; 516005) expression. No mtDNA variant in the D-loop appeared to be involved. Savagner et al. (2003) concluded that overexpression of the PRC pathway is responsible for mitochondrial proliferation in the context of thyroid oncocytoma.
By analysis of a human/rodent somatic cell hybrid panel, Nagase et al. (1998) mapped the KIAA0595 gene (PPRC1) to chromosome 10.
Andersson and Scarpulla (2001) mapped the PPRC1 gene to chromosome 10q24.2-q24.3.
Andersson, U., Scarpulla, R. C. PGC-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Molec. Cell. Biol. 21: 3738-3749, 2001. [PubMed: 11340167] [Full Text: https://doi.org/10.1128/MCB.21.11.3738-3749.2001]
Chengye, Z., Daixing, Z., Qiang, Z., Shusheng, L. PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF-kappaB activity. Biochem. Biophys. Res. Commun. 439: 121-125, 2013. [PubMed: 23954632] [Full Text: https://doi.org/10.1016/j.bbrc.2013.08.015]
Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 31-39, 1998. [PubMed: 9628581] [Full Text: https://doi.org/10.1093/dnares/5.1.31]
Savagner, F., Mirebeau, D., Jacques, C., Guyetant, S., Morgan, C., Franc, B., Reynier, P., Malthiery, Y. PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma. Biochem. Biophys. Res. Commun. 310: 779-784, 2003. [PubMed: 14550271] [Full Text: https://doi.org/10.1016/j.bbrc.2003.09.076]