Thioredoxin-Binding Protein-2-Like Inducible Membrane Protein Is a Novel Vitamin D3 and Peroxisome Proliferator-Activated Receptor (PPAR)γ Ligand Target Protein that Regulates PPARγ Signaling

Abstract

Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-γ, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and -independent cell growth and PPARγ ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARγ ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARγ activation.