Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14.

Tumor Progression and Metastasis Program, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
Phosphoglucose isomerase (PGI; EC is a ubiquitous cytosolic enzyme essential for glycolysis and gluconeogenesis. PGI is a multifunctional dimeric protein that extracellularly acts as a cytokine [autocrine motility factor (AMF)] eliciting mitogenic, motogenic, and differentiation functions through binding to its cell surface receptor gp78/AMF receptor (AMFR). AMFR contains a seven-transmembrane domain with RING-H2 and leucine zipper motifs showing ubiquitin protein ligase (E3) activity and is exposed on the endoplasmic reticulum surface. Augmented expressions of both PGI/AMF and AMFR have been implicated in tumor progression and metastasis, and an intracellular binding partner of PGI/AMF is expected to regulate in part its diverse biological functions. Thus, we screened a cDNA library using a yeast two-hybrid system to search for interacting protein(s) and report on the finding of poly(ADP-ribose) polymerase-14 (PARP-14) to be a binding partner with PGI/AMF. PARP-14-PGI/AMF interaction was confirmed by coimmunoprecipitation and immunolocalization. We also report that PGI/AMF degradation is mainly regulated by the ubiquitin-lysosome system and RNA interference experiments revealed that PARP-14 inhibits PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. This newly characterized PARP-14 protein should assist in understanding the regulation of PGI/AMF intracellular function(s) and may provide a new therapeutic target for inhibition of PGI/AMF inducing tumor cell migration and invasion during metastasis.
Mesh Terms:
Autocrine Motility Factor, Bone Neoplasms, Colonic Neoplasms, DNA, Complementary, Endothelial Cells, Fibrosarcoma, Glucose-6-Phosphate Isomerase, HT29 Cells, Humans, Osteosarcoma, Poly(ADP-ribose) Polymerases
Cancer Res. Sep. 15, 2007; 67(18);8682-9 [PUBMED:17875708]
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