Full Text:  <683>

CLC number: Q74; R34

On-line Access: 2013-03-06

Received: 2012-12-24

Revision Accepted: 2013-02-17

Crosschecked: 2013-02-18

Cited: 0

Clicked: 1156

Citations:  Bibtex RefMan EndNOte GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.3 P.171-177

doi: 10.1631/jzus.B1200357


Recent advances in the study of testicular nuclear receptor 4


Author(s):  Xian-fan Ding, Shi-cheng Yu, Bi-de Chen, Shin-jen Lin, Chawnshang Chang, Gong-hui Li

Affiliation(s):  1.Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester, New York 14642, USA

Corresponding email(s):  chang@urmc.rochester.edu , ligonghui1970@hotmail.com

Key Words:  NR2C2, TR4, Nuclear receptor, Gene knock out


Share this article to? More

Xian-fan Ding, Shi-cheng Yu, Bi-de Chen, Shin-jen Lin, Chawnshang Chang, Gong-hui Li. Recent advances in the study of testicular nuclear receptor 4[J]. Journal of Zhejiang University Science B, 2013, 1(14): 171-177.

@article{0
title="Recent advances in the study of testicular nuclear receptor 4",
author="Xian-fan Ding, Shi-cheng Yu, Bi-de Chen, Shin-jen Lin, Chawnshang Chang, Gong-hui Li",
journal="Journal of Zhejiang University Science B",
volume="14",
number="1",
pages="171-177",
year="2013",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1200357"
}

%0 Journal Article
%T Recent advances in the study of testicular nuclear receptor 4
%A Xian-fan Ding
%A Shi-cheng Yu
%A Bi-de Chen
%A Shin-jen Lin
%A Chawnshang Chang
%A Gong-hui Li
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 1
%P 171-177
%@ 1673-565X
%D 2013
%I Zhejiang University Press & Springer

TY - JOUR
T1 - Recent advances in the study of testicular nuclear receptor 4
A1 - Xian-fan Ding
A1 - Shi-cheng Yu
A1 - Bi-de Chen
A1 - Shin-jen Lin
A1 - Chawnshang Chang
A1 - Gong-hui Li
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 1
SP - 0
EP - 0
SN - 1673-565X
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -


Abstract: 
Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4’s physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4−/−) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4−/− phenotype. With the establishment of a tissue-specific TR4−/− mouse model, research on TR4 will be more convenient in the future.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Aranda, A., Pascual, A., 2001. Nuclear hormone receptors and gene expression. Physiol. Rev., 81(3):1269-1304.

[2]Bowen, R.L., Atwood, C.S., 2004. Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. Gerontology, 50(5):265-290.

[3]Campbell, A.D., Cui, S., Shi, L., Urbonya, R., Mathias, A., Bradley, K., Bonsu, K.O., Douglas, R.R., Halford, B., Schmidt, L., et al., 2011. Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. PNAS, 108(46):18808-18813.

[4]Chang, C., da Silva, S.L., Ideta, R., Lee, Y., Yeh, S., Burbach, J.P., 1994. Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily. PNAS, 91(13):6040-6044.

[5]Chen, L.M., Wang, R.S., Lee, Y.F., Liu, N.C., Chang, Y.J., Wu, C.C., Xie, S., Hung, Y.C., Chang, C., 2008. Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4. Mol. Endocrinol., 22(4):858-867.

[6]Chen, Y.T., Collins, L.L., Chang, S.S., Chang, C., 2008. The roles of testicular orphan nuclear receptor 4 (TR4) in cerebellar development. Cerebellum, 7(1):9-17.

[7]Choi, H., Kim, S.J., Park, S.S., Chang, C., Kim, E., 2011. TR4 activates FATP1 gene expression to promote lipid accumulation in 3T3-L1 adipocytes. FEBS Lett., 585(17):2763-2767.

[8]Collins, L.L., Lee, Y.F., Heinlein, C.A., Liu, N.C., Chen, Y.T., Shyr, C.R., Meshul, C.K., Uno, H., Platt, K.A., Chang, C., 2004. Growth retardation and abnormal maternal behavior in mice lacking testicular orphan nuclear receptor 4. PNAS, 101(42):15058-15063.

[9]Collins, L.L., Lee, Y.F., Ting, H.J., Lin, W.J., Liu, N.C., Meshul, C.K., Uno, H., Bao, B.Y., Chen, Y.T., Chang, C., 2011. The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice. Reprod. Biol. Endocrinol., 9(1):138.

[10]Cui, S., Kolodziej, K.E., Obara, N., Amaral-Psarris, A., Demmers, J., Shi, L., Engel, J.D., Grosveld, F., Strouboulis, J., Tanabe, O., 2011. Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells. Mol. Cell. Biol., 31(16):3298-3311.

[11]Harada, H., Kuboi, Y., Miki, R., Honda, C., Masushige, S., Nakatsuka, M., Koga, Y., Kato, S., 1998. Cloning of rabbit TR4 and its bone cell-specific activity to suppress estrogen receptor-mediated transactivation. Endocrinology, 139(1):204-212.

[12]Hirose, T., Fujimoto, W., Tamaai, T., Kim, K.H., Matsuura, H., Jetten, A.M., 1994. TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily. Mol. Endocrinol., 8(12):1667-1680.

[13]Huang, Y.H., Liao, C.H., Chen, R.N., Liao, C.J., Lin, K.H., 2010. Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling. J. Cell. Physiol., 222(2):347-356.

[14]Kang, H.S., Okamoto, K., Kim, Y.S., Takeda, Y., Bortner, C.D., Dang, H., Wada, T., Xie, W., Yang, X.P., Liao, G., et al., 2011. Nuclear orphan receptor TAK1/TR4-deficient mice are protected against obesity-linked inflammation, hepatic steatosis, and insulin resistance. Diabetes, 60(1):177-188.

[15]Kim, E., Xie, S., Yeh, S.D., Lee, Y.F., Collins, L.L., Hu, Y.C., Shyr, C.R., Mu, X.M., Liu, N.C., Chen, Y.T., et al., 2003. Disruption of TR4 orphan nuclear receptor reduces the expression of liver apolipoprotein E/C-I/C-II gene cluster. J. Biol. Chem., 278(47):46919-46926.

[16]Kim, E., Yang, Z., Liu, N.C., Chang, C., 2005. Induction of apolipoprotein E expression by TR4 orphan nuclear receptor via 5′ proximal promoter region. Biochem. Biophys. Res. Commun., 328(1):85-90.

[17]Kim, E., Liu, N.C., Yu, I.C., Lin, H.Y., Lee, Y.F., Sparks, J.D., Chen, L.M., Chang, C., 2011. Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-COA desaturase 1 gene expression with altered insulin sensitivity. Diabetes, 60(5):1493-1503.

[18]Lee, H.J., Lee, Y.F., Chang, C., 2001. TR4 orphan receptor represses the human steroid 21-hydroxylase gene expression through the monomeric AGGTCA motif. Biochem. Biophys. Res. Commun., 285(5):1361-1368.

[19]Lee, Y.F., Young, W.J., Burbach, J.P., Chang, C., 1998. Negative feedback control of the retinoid-retinoic acid/ retinoid X receptor pathway by the human TR4 orphan receptor, a member of the steroid receptor superfamily. J. Biol. Chem., 273(22):13437-13443.

[20]Lee, Y.F., Young, W.J., Lin, W.J., Shyr, C.R., Chang, C., 1999. Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor. J. Biol. Chem., 274(23):16198-16205.

[21]Lee, Y.F., Lee, H.J., Chang, C., 2002. Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily. J. Steroid Biochem. Mol. Biol., 81(4-5):291-308.

[22]Lee, Y.F., Liu, S., Liu, N.C., Wang, R.S., Chen, L.M., Lin, W.J., Ting, H.J., Ho, H.C., Li, G., Puzas, E.J., et al., 2011. Premature aging with impaired oxidative stress defense in mice lacking TR4. Am. J. Physiol. Endocrinol. Metab., 301(1):E91-E98.

[23]Li, G., Lee, Y.F., Liu, S., Cai, Y., Xie, S., Liu, N.C., Bao, B.Y., Chen, Z., Chang, C., 2008. Oxidative stress stimulates testicular orphan receptor 4 through forkhead transcription factor forkhead box O3a. Endocrinology, 149(7):3490-3499.

[24]Lin, S.J., Ho, H.C., Lee, Y.F., Liu, N.C., Liu, S., Li, G., Shyr, C.R., Chang, C., 2012. Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis. Reprod. Biol. Endocrinol., 10(1):43.

[25]Liu, N.C., Lin, W.J., Kim, E., Collins, L.L., Lin, H.Y., Yu, I.C., Sparks, J.D., Chen, L.M., Lee, Y.F., Chang, C., 2007. Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis. Diabetes, 56(12):2901-2909.

[26]Liu, S., Lee, Y.F., Chou, S., Uno, H., Li, G., Brookes, P., Massett, M.P., Wu, Q., Chen, L.M., Chang, C., 2011a. Mice lacking TR4 nuclear receptor develop mitochondrial myopathy with deficiency in complex I. Mol. Endocrinol., 25(8):1301-1310.

[27]Liu, S., Yan, S.J., Lee, Y.F., Liu, N.C., Ting, H.J., Li, G., Wu, Q., Chen, L.M., Chang, C., 2011b. Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via cockayne syndrome B protein-mediated transcription-coupled DNA repair. J. Biol. Chem., 286(44):38103-38108.

[28]Mu, X., Lee, Y.F., Liu, N.C., Chen, Y.T., Kim, E., Shyr, C.R., Chang, C., 2004. Targeted inactivation of testicular nuclear orphan receptor 4 delays and disrupts late meiotic prophase and subsequent meiotic divisions of spermatogenesis. Mol. Cell. Biol., 24(13):5887-5899.

[29]Popov, V.M., Wang, C., Shirley, L.A., Rosenberg, A., Li, S., Nevalainen, M., Fu, M., Pestell, R.G., 2007. The functional significance of nuclear receptor acetylation. Steroids, 72(2):221-230.

[30]Robinson-Rechavi, M., Escriva Garcia, H., Laudet, V., 2003. The nuclear receptor superfamily. J. Cell. Sci., 116(Pt 4):585-586.

[31]Shyr, C.R., Kang, H.Y., Tsai, M.Y., Liu, N.C., Ku, P.Y., Huang, K.E., Chang, C., 2009. Roles of testicular orphan nuclear receptors 2 and 4 in early embryonic development and embryonic stem cells. Endocrinology, 150(5):2454-2462.

[32]Tanabe, O., Katsuoka, F., Campbell, A.D., Song, W., Yamamoto, M., Tanimoto, K., Engel, J.D., 2002. An embryonic/fetal β-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer. EMBO J, 21(13):3434-3442.

[33]Tsai, N.P., Huq, M., Gupta, P., Yamamoto, K., Kagechika, H., Wei, L.N., 2009. Activation of testicular orphan receptor 4 by fatty acids. Biochim. Biophys. Acta, 1789(11-12):734-740.

[34]Wang, C.P., Lee, Y.F., Chang, C., Lee, H.J., 2006. Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor. Biochem. Biophys. Res. Commun., 351(1):204-208.

[35]Xie, S., Lee, Y.F., Kim, E., Chen, L.M., Ni, J., Fang, L.Y., Liu, S., Lin, S.J., Abe, J., Berk, B., et al., 2009. TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation. PNAS, 106(32):13353-13358.

[36]Xie, S., Ni, J., Lee, Y.F., Liu, S., Li, G., Shyr, C.R., Chang, C., 2011. Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation. J. Biol. Chem., 286(24):21129-21136.

[37]Yan, S.J., Lee, Y.F., Ting, H.J., Liu, N.C., Liu, S., Lin, S.J., Yeh, S.D., Li, G., Chang, C., 2012. Deficiency in TR4 nuclear receptor abrogates GADD45A expression and increases cytotoxicity induced by ionizing radiation. Cell Mol. Biol. Lett., 17(2):309-322.

[38]Yan, Z.H., Karam, W.G., Staudinger, J.L., Medvedev, A., Ghanayem, B.I., Jetten, A.M., 1998. Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J. Biol. Chem., 273(18):10948-10957.

[39]Yang, X., Downes, M., Yu, R.T., Bookout, A.L., He, W., Straume, M., Mangelsdorf, D.J., Evans, R.M., 2006. Nuclear receptor expression links the circadian clock to metabolism. Cell, 126(4):801-810.

[40]Zhang, Y., Dufau, M.L., 2000. Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor. J. Biol. Chem., 275(4):2763-2770.

[41]Zhou, X.E., Suino-Powell, K.M., Xu, Y., Chan, C.W., Tanabe, O., Kruse, S.W., Reynolds, R., Engel, J.D., Xu, H.E., 2011. The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J. Biol. Chem., 286(4):2877-2885.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952276; Fax: +86-571-87952331; E-mail: jzus@zju.edu.cn
Copyright © 2000~ Journal of Zhejiang University-SCIENCE