Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spliceosomal cyclophilin H is a specific component of the human U4/U6 small nuclear ribonucleoprotein particle, interacting with homologous sequences in the proteins U4/U6-60K and hPrp18 during pre-mRNA splicing. We determined the crystal structure of the complex comprising cyclophilin H and the cognate domain of U4/U6-60K. The 31 amino acid fragment of U4/U6-60K is bound to a region remote from the cyclophilin active site. Residues Ile118-Phe121 of U4/U6-60K expand the central beta-sheet of cyclophilin H and the side-chain of Phe121 inserts into a hydrophobic cavity. Concomitantly, in the crystal the cyclophilin H active site is occupied by the N terminus of a neighboring cyclophilin H molecule in a substrate-like manner, indicating the capacity of joint binding to a substrate and to U4/U6-60K. Free and complexed cyclophilin H have virtually identical conformations suggesting that the U4/U6-60K binding site is pre-shaped and the peptidyl-prolyl-cis/trans isomerase activity is unaffected by complex formation. The complex defines a novel protein-protein interaction mode for a cyclophilin, allowing cyclophilin H to mediate interactions between different proteins inside the spliceosome or to initiate from its binding platforms isomerization or chaperoning activities.
J Mol Biol 2003 Aug 01
PMID:Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide. 1287 35

Pre-mRNA processing factor 4 (PRPF4), a core protein in U4/U6 snRNP, maintains snRNP structures by interacting with PRPF3 and cyclophilin H. Expression of the PRPF4 gene affects cell survival as well as apoptosis and is responsible for retinitis pigmentosa (RP). Proteomics analysis shows that PRPF4 may be a therapeutic target in human cancers. Nevertheless, the exact function and role of the PRPF4 gene are unclear. In this study, we assessed the expression of PRPF4 gene in human breast cancer cells. First, we confirmed that the PRPF4 gene was overexpressed in various breast cancer cell lines. Next, using breast cancer cell lines MCF7 and MDA-MB-468, we established stable cell lines with PRPF4 gene knockdown. We also performed microarray analysis to investigate molecular mechanisms underlying PRPF4 activity. All cell lines with PRPF4 gene knockdown exhibited reduced cell proliferation, remarkable reduction in anchorage-independent colony formation capacity, and reduction of PCNA protein, which is a marker cell of proliferation. Reduced expression of the PRPF4 gene induced apoptosis and changes in the expression of associated apoptotic markers in breast cancer cell lines. Knockdown of the PRPF4 gene reduced cellular capacity for migration and invasion (the key hallmarks of human cancers) and decreased the expression of genes involved in epithelial-mesenchymal transition (EMT). Microarray results showed that the expression of PPIP5K1, PPIPK2, and YWHAE genes was reduced at the transcriptional level, leading to reduced phosphorylation of p38 MAPK. These findings suggest that knockdown of PRPF4 gene slows down breast cancer progression via suppression of p38 MAPK phosphorylation. In conclusion, the PRPF4 gene plays an important role in the growth of breast cancer cells and is therefore a potential therapeutic target.
Mol Cell Probes 2019 10
PMID:PRPF4 is a novel therapeutic target for the treatment of breast cancer by influencing growth, migration, invasion, and apoptosis of breast cancer cells via p38 MAPK signaling pathway. 3144 70