Details

Autor(en) / Beteiligte

• VIDAL, Hubert
• MONDESERT, Guillaume
• LOISON, Gérard
• CASELLAS, Pierre
• GALIEGUE, Sylvaine
• CARRIERE, Dominique
• DUPUY, Pascal-Henri
• CARAYON, Pierre
• COMBES, Thérèse
• BRIBES, Estelle
• SIMONY-LAFONTAINE, Joëlle
• KRAMAR, Andrew

Titel

Identification and pharmacological characterization of SRBP-2: A novel SR31747A-binding protein

Ist Teil von

• Cancer research (Chicago, Ill.), 2003-08, Vol.63 (16), p.4809-4818

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2003

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• SR31747A is a sigma ligand with potent antiproliferative activity against tumor cells and for which three binding proteins have been identified to date: (a) SRBP-1 (also called sigma 1); (b) HIS; and (c) sigma 2. In this study, we characterized an additional SR31747A binding site, i.e., SRBP-2 (SR31747A-binding protein 2). Using an in silico screening approach, we identified this novel sequence, which exhibits 41% homology with HSI. The 1142-bp cDNA was found to encode a 206 amino acid protein not related to SRBP-1. Northern blot analysis of SRBP-2 mRNA expression revealed a single 1.1-kb transcript that was widely expressed in organs; the liver was particularly enriched, and the brain showed the lowest abundance. A murine homologue that exhibited a similar expression pattern was also characterized. Subcellular localization analysis using specific polyclonal antibodies revealed that SRBP-2 had the same nuclear membrane and endoplasmic reticulum localization as other members of the SR31747A-binding protein family. Considering SRBP-2-binding properties, pharmacological analysis clearly highlighted that SRBP-2 was distinct from sigma 2. Scatchard plot analysis revealed K(d) values of 10 and 3 nM for SR31747A and Tamoxifen, respectively. In contrast with HSI, the protein also did not exhibit detectable isomerase activity. When analyzing SRBP-2 expression in human breast cancer biopsies, we obtained evidence that SRBP-2 expression, together with SRBP-1 and HSI, may be of interest as a prognostic marker. These findings demonstrated that SRBP-2 represents an additional molecular target for SR31747A, which could help to understand the immunosuppressive and antiproliferative effects of the molecule.