Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR)gamma ligand target protein that regulates PPARgamma signaling

Endocrinology. 2006 Feb;147(2):733-43. doi: 10.1210/en.2005-0679. Epub 2005 Nov 3.

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)-gamma, 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 PPARgamma ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARgamma ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARgamma activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arrestins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cell Proliferation*
  • Endosomes / metabolism
  • Humans
  • Lysosomes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • PPAR gamma / metabolism*
  • RNA, Messenger / analysis
  • Receptors, Calcitriol / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*

Substances

  • ARRDC3 protein, human
  • Arrestins
  • Carrier Proteins
  • Membrane Proteins
  • PPAR gamma
  • RNA, Messenger
  • Receptors, Calcitriol
  • TXNIP protein, human
  • Thioredoxins