Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14.
Phosphoglucose isomerase (PGI; EC 5.3.1.9) 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.
Yanagawa
Takashi
T
Tumor Progression and Metastasis Program, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
Funasaka
Tatsuyoshi
T
Tsutsumi
Soichi
S
Hu
Huankai
H
Watanabe
Hideomi
H
Raz
Avraham
A
D001859:Bone Neoplasms / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D042783:Endothelial Cells / Q000201:enzymology; D005354:Fibrosarcoma / Q000201:enzymology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D012516:Osteosarcoma / Q000201:enzymology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D011065:Poly(ADP-ribose) Polymerases; D005956:Glucose-6-Phosphate Isomerase