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
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
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DOI：
10.1210/en.2005-0679
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发表时间：
2006-02-01
期刊：
影响因子：
4.8
通讯作者：
Yodoi, J
中科院分区：
文献类型：
--
作者：
Oka, S;Masutani, H;Yodoi, J
硫氧还蛋白结合蛋白-2（TBP-2）与维生素D3（VD 3）上调蛋白1（VDUP 1）相同，在糖脂代谢整合中起着至关重要的作用。TBP-2/维生素D3上调蛋白1在人类中有3个高度同源的基因，但其功能尚不清楚。在这里，我们表征了TBP-2同源物，TBP-2样诱导膜蛋白（TLIMP）。与TBP-2相反，TLIMP对硫氧还蛋白没有显示出显著的结合亲和力。TLIMP表现出内膜相关的分布模式，并与转铁蛋白和低密度脂蛋白共定位，表明内体和溶酶体相关的功能。VD 3和过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）-γ（一种重要的能量代谢和细胞生长抑制调节剂）的配体诱导了TLIMP和TBP-2的表达。TLIMP的过表达抑制了锚定依赖性和非依赖性细胞生长和PPAR γ配体诱导的基因激活。这些结果表明，TLIMP，一种新的VD 3或PPAR γ配体诱导的膜相关蛋白，在细胞增殖和PPAR γ激活中起着调节作用。
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 PPAR gamma ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPAR gamma ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPAR gamma activation.