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.
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.
Oka
Shin-ichi
S
Institute for Virus Research, Kyoto University, Japan.
Masutani
Hiroshi
H
Liu
Wenrui
W
Horita
Hiroyuki
H
Wang
Dongmei
D
Kizaka-Kondoh
Shinae
S
Yodoi
Junji
J
D000595:Amino Acid Sequence; D019390:Arrestins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
C508469:ARRDC3 protein, human; D019390:Arrestins; D002352:Carrier Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C486715:TXNIP protein, human; D013879:Thioredoxins