ISSN 1007-7626 CN 11-3870 / Q http / / cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology 2012 3 28 3 222 ~ 226 TXNIP 1 * 2 1 510515 2 510515 thioredoxin-interacting proteintxnip TXNIP thioredoxintrx Trx Trx DNA TXNIP TXNIP TXNIP TXNIP TXNIP NK natural killer cellnk cell TXNIP Trx R73 TXNIP Gene in Tumorigenesis and Metastasis LI Li-Fu 1 * LIANG Li 2 1 First Clinical Medical College of Southern Medical UniversityGuangzhou 2 Department of Pathology of Southern Medical UniversityGuangzhou 510515China 510515China Abstract Thioredoxin-interacting protein TXNIP is a multifunctional protein that is involved in cell proliferationapoptosisand differentiation TXNIP is also related to cancers and other stress-related diseases As a major redox regulatortxnip interacts with thioredoxin Trx and negatively regulates Trx expression and its antioxidant function which is critical in DNA damage and apoptosis This review will overview the TXNIP gene functions for its strongly association with tumorigenesismetastasis and its commonly reduced expression in tumor tissuessuch as breastlungand liver cancers TXNIP deficiency increases cell proliferation and protects the cells from apoptosis We discuss various molecular mechanisms with the reports of TXNIP signaling and biological functionsincluding cell cycle arrest hypoxia and NK developmentwhich explain the tumor suppressive role of TXNIP Key words thioredoxin-interacting protein TXNIP thioredoxin Trx tumor metastasis thioredoxin-interacting D-3 HL-60 protein TXNIP D3 1 3 TXNIP vitamin D3 up-regulating protein 1 VDUP1 α- thioredoxin TXNIP Trx 1 2011-09-19 2011-12-29 No 30870945 Trx * Tel 13268379472 E-mail 1037051347@ qq com Received September 19 2011 Accepted December 29 2011 Supported by National Natural Science Foundation of China No 30870945 2 TXNIP TXNIP 1q21-22 8 4 174 bp TXNIP 1 25 NK * Corresponding author Tel 13268379472 E-mail 1037051347@ qq com
3 TXNIP 223 TXNIP 1 HTLV-1 T TXNIP 1 TXNIP TXNIP TXNIP Trx NK 4 TXNIP Trx TXNIP TXNIP Trx 5 1 1 3 TXNIP apoptosis signal- regulating kinase 1 ASKⅠ mitogen-activated protein kinase MAPK 4 6 TXNIP TXNIP 3 calcitonin receptor-stimulating peptide 3 TXNIP CRSP3 15 Kiss1 HGMW-approved symbol 2 TXNIP TXNIP TXNIP TXNIP Kiss1 KISS1 CRSP3 Kiss1 TXNIP Song 7 TXNIP TXNIP CRSP3 Kiss1 cdna FasL CD44 TXNIP TXNIP - β Turturro 16 d- 9 TXNIP 6 h TXNIP 10 d- Trx TXNIP 11 17 TXNIP d- TXNIP G 1 TXNIP 1 chromosome RT-PCR region maintenance 1 protein CRM1 TXNIP 12 TXNIP 1α hypoxia-inducible factor 1α HIF1α 18 HIF1α 1 TXNIP VHL Von Hippel-Lindau TXNIP protein pvhl TXNIP 13 TXNIP pvhl β pvhl HIF1α TXNIP HIF1α TXNIP T pvhl / HIF1α HIF1α 1 human T lymphotropic virus type- T ATL 14 TXNIP TXNIP
224 28 4 TXNIP Fig 1 TXNIP Trx NK 1 TXNIP 3 Fig 1 TXNIP signaling pathways and tumor suppressive functions TXNIP is involved in a variety of cellular function including NK developmentgrowth inhibition apoptosis in Trx-mediated antioxidant function and modulating other molecules such as CRSP3 Kiss1 and CRM1 signs indicate activation and signs indicate inhibition 4 1 TXNIP TXNIP Northern G 0 /G 1 TXNIP TXNIP TXNIP TXNIP 19 TXNIP A cyclin A p16 p27kip TXNIP cyclin A 20 TXNIP pvhl HIF1α TXNIP p16 T 18 21 p27 1 p27 kinase inhibition protein 1 p27kip1 1 G 1 / S TXNIP carbohydrate response Jun 1 Jun activation domain-binding elementchores protein1 jab1 p27kip1 24 MLX ChoREs jab1 p27kip1 Le Jan 23 133 HIF1α pvhl MAX X MAX-like protein X MLX G 1 / S 22 TXNIP 25 TXNIP TXNIP 1 TXNIP 4 2 TXNIP 4 3 TXNIP NK TXNIP NK
3 TXNIP 225 NK J TXNIP NK 26 NK TXNIP NK cancer cells J TXNIP NK T CTL CD8 + 27 TXNIP 5 TXNIP 1 25- OH 2 D 3 HL- 60 Trx TXNIP TXNIP TXNIP 1 TXNIP 3 TXNIP CRSP3 Kiss1 TXNIP TXNIP HIF1α TXNIP TXNIP TXNIP NK and its relation to stage of diseasej Trx 6C 4045-4048 TXNIP overexpressed in a subset of aml patients J 33 10 1367-1371 References 1 Zhou JYu QChng W J Txnip vdup-1tbp-2 A major redox regulator commonly suppressed in cancer by epigenetic mechanisms J Int J Biochem Cell Biol201143 12 1668-1673 2 Le Bras MClement M VPervaiz Set al Reactive oxygen species and the mitochondrial signaling pathway of cell death J Histol Histopathol200520 1 205-219 3 Chen K SDeluca H F Isolation and characterization of a novel cdna from hl-60 cells treated with 1 25-dihydroxyvitamin d-3 Biochim Biophys Acta19941219 1 26-32 4 Kim S YSuh H WChung J Wet al Diverse functions of vdup1 in cell proliferationdifferentiationand diseases J Cell Mol Immunol20074 5 345-351 5 Lee J HJeong E GChoi M Cet al Inhibition of histone deacetylase 10 induces thioredoxin- interacting protein and causes accumulation of reactive oxygen species in snu-620 human gastric Mol Cells201030 2 107-112 6 Stoltzman C AKaadige M RPeterson C Wet al Mondoa senses non-glucose sugars Regulation of txnip and the hexose transport curb J J Biol Chem2011 286 44 38027-38034 7 Song HCho DJeon J Het al Vitamin d 3 up-regulating protein 1 vdup1 antisense DNA regulates tumorigenicity and melanogenesis of murine melanoma cells via regulating the expression of fas ligand and reactive oxygen species J Immunol Lett200386 3 235-347 8 Vaira SFriday EScott Ket al Wnt / beta-catenin signalling pathway and thioredoxin- interacting protein txnip mediate the glucose sensor mechanism in metastatic breast cancer derived cells mda-mb-231 J J Cell Physiol2012227 2 578-586 9 Yamaguchi FTakata MKamitori Ket al Rare sugar d-allose induces specific up-regulation of txnip and subsequent g1 cell cycle arrest in hepatocellular carcinoma cells by stabilization of p27kip1 J Int J Oncol200832 2 377-385 10Sheth S SBodnar J SGhazalpour Aet al Hepatocellular carcinoma in txnip-deficient mice J Oncogene200625 25 3528-3536 11Hoshikawa HMori TMori N In vitro and in vivo effects of d- allose Up-regulation of thioredoxin-interacting protein in head and neck cancer cells J Ann Otol Rhinol Laryngol 2010119 8 567-571 12Ikarashi MTakahashi YIshii Yet al Vitamin d3 upregulated protein 1 vdup1 expression in gastrointestinal cancer Anticancer Res 2002 22 13Erkeland S JPalande K KValkhof Met al The gene encoding thioredoxin-interacting protein txnip is a frequent virus integration site in virus-induced mouse leukemia and is Leuk Res2009 14Chen ZLopez-Ramos D AYoshihara Eet al Thioredoxinbinding protein-2 tbp-2 / vdup1 / txnip regulates t-cell sensitivity to glucocorticoid during htlv-i-induced transformation J Leukemia201125 3 440-448 15Goldberg S FMiele M EHatta Net al Melanoma metastasis suppression by chromosome 6 Evidence for a pathway regulated by crsp3 and txnip J Cancer Res200363 2 432-440 16Turturro FFriday EWelbourne T Hyperglycemia regulates thioredoxin-ros activity through induction of thioredoxininteracting protein txnip in metastatic breast cancer- derived cells mda-mb-231 J BMC Cancer20077 96
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