Research progress on the involvement of nuclear receptor in regulating autophagy_Journal of Biomedical Engineering

Authors：

WU Lingjuan , XU Xiaoli , LIN Jun , CAI Weiwen ,  CHEN Liqun

College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, P.R.China;

Corresponding author：

Keywords：

nuclear receptor; autophagy; nerve growth factor-induced gene B; retinoic acid receptor; vitamin D receptor; farnesoid X receptor

DOI：

10.7507/1001-5515.201804028

Video：

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Nuclear receptors are transcriptional regulators involved in almost all biological processes such as cell growth, differentiation, apoptosis, substance metabolism and tumor formation, and they can be regulated by small molecules that bind to them. Autophagy is a special way of programmed cell death and it is a highly conserved metabolic process. Once autophagy defects or excessive autophagy occur, the disease will develop. In recent years, numerous studies have shown that nuclear receptors are related to autophagy. Therefore, this paper mainly reviews the research progress on nuclear receptors involved in the regulation of autophagy, and focuses on the mechanism of several nuclear receptors involved in the regulation of autophagy, aiming at understanding the molecular basis of how nuclear receptors participate in regulating autophagy, as well as providing possible ideas and strategies for the treatment of corresponding diseases.

Citation： WU Lingjuan, XU Xiaoli, LIN Jun, CAI Weiwen, CHEN Liqun. Research progress on the involvement of nuclear receptor in regulating autophagy. Journal of Biomedical Engineering, 2018, 35(5): 822-828. doi: 10.7507/1001-5515.201804028 Copy

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2.	de Mattia E, Cecchin E, Roncato R, et al. Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine. Pharmacogenomics, 2016, 17(14): 1547-1571.
3.	Tanaka N, Aoyama T, Kimura S, et al. Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol Ther, 2017, 179: 142-157.
4.	Wall C E, Yu R T, Atkins A R, et al. Nuclear receptors and AMPK: can exercise mimetics cure diabetes?. Journal of molecular endocrinology, 2016, 57(1): R49-R58.
5.	Ajith T A, Jayakumar T G. Peroxisome proliferator-activated receptors in cardiacenergy metabolism and cardiovascular disease. Clinical and Experimental Pharmacology and Physiology, 2016, 43(7): 649-658.
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7.	Crowder M K, Seacrist C D, Blind R D. Phospholipid regulation of the nuclear receptor superfamily. Adv Biol Regul, 2017, 63: 6-14.
8.	Wang Weijia, Wang Yuan, Chen Hangzi, et al. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014, 10(2): 133-140.
9.	Zhang Xiaokun, Zhou Hu, Su Ying. Targeting truncated RXR alpha for cancer therapy. Acta Biochim Biophys Sin (Shanghai), 2016, 48(1): 49-59.
10.	Chen L, Aleshin A E, Alitongbieke G, et al. Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRalpha. Nature communications, 2017, 8: 16066.
11.	Ghosh R, Pattison J S. Macroautophagy and chaperone-mediated autophagy in heart failure: the known and the unknown. Oxid Med Cell Longev, 2018, 2018(1): 8602041.
12.	Nascimbeni A C, Codogno P, Morel E. Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J, 2017, 284(9): 1267-1278.
13.	Arakawa S, Honda S, Yamaguchi H, et al. Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proc Jpn Acad Ser B Phys Biol Sci, 2017, 93(6): 378-385.
14.	Wen Xin, Klionsky D J. An overview of macroautophagy in yeast. J Mol Biol, 2016, 428(9 Pt A): 1681-1699.
15.	Nishida Yuya, Arakawa S, Fujitani K, et al. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature, 2009, 461(7264): 654-658.
16.	Shimizu Shigeomi. Biological roles of alternative autophagy. Mol Cells, 2018, 41(1): 50-54.
17.	Hu Mengjie, Luo Qiang, Alitongbieke Gulimiran, et al. Celastrol-induced Nur77 interaction with TRAF2 alleviates inflammation by promoting mitochondrial ubiquitination and autophagy. Mol Cell, 2017, 66(1): 141-153.
18.	Zhong Chen, Pu Liyong, Fang Mingming, et al. Retinoic acid receptor alpha promotes autophagy to alleviate liver ischemia and reperfusion injury. World Journal of Gastroenterology, 2015, 21(43): 12381-12391.
19.	Brigger D, Schlafli A M, Garattini E, et al. Activation of RARalpha induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity. Cell, 2015, 6: e1861.
20.	Yao Tianbao, Ying Xiaoying, Zhao Yichao, et al. Vitamin D receptor activation protects against myocardial reperfusion injury through inhibition of apoptosis and modulation of autophagy. Antioxid Redox Signal, 2015, 22(8): 633-650.
21.	Cui Changmeng, Cui Jianzhong, Jin Feng, et al. Induction of the vitamin D receptor attenuates autophagy dysfunction-mediated cell death following traumatic brain injury. Cell Physiol Biochem, 2017, 42(5): 1888-1896.
22.	Sun Jun. VDR/vitamin D receptor regulates autophagic activity through ATG16L1. Autophagy, 2016, 12(6): 1057-1058.
23.	Abdel-Mohsen M A, El-Braky A A, Ghazal A A, et al. Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus. Medicine, 2018, 97(12): e0172.
24.	Tavera-Mendoza L E, Westerling T, Libby E, et al. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc Natl Acad Sci USA, 2017, 114(11): E2186-E2194.
25.	Seok S, Fu Ting, Choi S E, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature, 2014, 516(7529): 108-111.
26.	Lee J M, Wagner M, Xiao Rui, et al. Nutrient-sensing nuclear receptors coordinate autophagy. Nature, 2014, 516(7529): 112-115.
27.	Lee J M. Transcriptional coordination of hepatic autophagy by nutrient-sensing nuclear receptor PPARalpha and FXR. Annals of Pediatric Endocrinology Metabolism, 2016, 21(4): 193-198.
28.	Zhou Xiaodong, Xie Li, Bergmann F, et al. The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis. Cell Death Discovery, 2017(3): 17027.
29.	Sun M M, Beier F, Ratneswaran A. Nuclear receptors as potential drug targets in osteoarthritis. Curr Opin Pharmacol, 2018, 40: 81-86.
30.	Zhang Lei, Liu Wen, Wang Qun, et al. New drug candidate targeting the 4A1 orphan nuclear receptor for medullary thyroid cancer therapy. Molecules, 2018, 23(3): 565.

1. Evans R M, Mangelsdorf D J. Nuclear receptors, RXR, and the Big Bang. Cell, 2014, 157(1): 255-266.
2. de Mattia E, Cecchin E, Roncato R, et al. Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine. Pharmacogenomics, 2016, 17(14): 1547-1571.
3. Tanaka N, Aoyama T, Kimura S, et al. Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol Ther, 2017, 179: 142-157.
4. Wall C E, Yu R T, Atkins A R, et al. Nuclear receptors and AMPK: can exercise mimetics cure diabetes?. Journal of molecular endocrinology, 2016, 57(1): R49-R58.
5. Ajith T A, Jayakumar T G. Peroxisome proliferator-activated receptors in cardiacenergy metabolism and cardiovascular disease. Clinical and Experimental Pharmacology and Physiology, 2016, 43(7): 649-658.
6. Mcewan I J. The nuclear receptor superfamily at thirty. Methods Mol Biol, 2016, 1443: 3-9.
7. Crowder M K, Seacrist C D, Blind R D. Phospholipid regulation of the nuclear receptor superfamily. Adv Biol Regul, 2017, 63: 6-14.
8. Wang Weijia, Wang Yuan, Chen Hangzi, et al. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014, 10(2): 133-140.
9. Zhang Xiaokun, Zhou Hu, Su Ying. Targeting truncated RXR alpha for cancer therapy. Acta Biochim Biophys Sin (Shanghai), 2016, 48(1): 49-59.
10. Chen L, Aleshin A E, Alitongbieke G, et al. Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRalpha. Nature communications, 2017, 8: 16066.
11. Ghosh R, Pattison J S. Macroautophagy and chaperone-mediated autophagy in heart failure: the known and the unknown. Oxid Med Cell Longev, 2018, 2018(1): 8602041.
12. Nascimbeni A C, Codogno P, Morel E. Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J, 2017, 284(9): 1267-1278.
13. Arakawa S, Honda S, Yamaguchi H, et al. Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proc Jpn Acad Ser B Phys Biol Sci, 2017, 93(6): 378-385.
14. Wen Xin, Klionsky D J. An overview of macroautophagy in yeast. J Mol Biol, 2016, 428(9 Pt A): 1681-1699.
15. Nishida Yuya, Arakawa S, Fujitani K, et al. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature, 2009, 461(7264): 654-658.
16. Shimizu Shigeomi. Biological roles of alternative autophagy. Mol Cells, 2018, 41(1): 50-54.
17. Hu Mengjie, Luo Qiang, Alitongbieke Gulimiran, et al. Celastrol-induced Nur77 interaction with TRAF2 alleviates inflammation by promoting mitochondrial ubiquitination and autophagy. Mol Cell, 2017, 66(1): 141-153.
18. Zhong Chen, Pu Liyong, Fang Mingming, et al. Retinoic acid receptor alpha promotes autophagy to alleviate liver ischemia and reperfusion injury. World Journal of Gastroenterology, 2015, 21(43): 12381-12391.
19. Brigger D, Schlafli A M, Garattini E, et al. Activation of RARalpha induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity. Cell, 2015, 6: e1861.
20. Yao Tianbao, Ying Xiaoying, Zhao Yichao, et al. Vitamin D receptor activation protects against myocardial reperfusion injury through inhibition of apoptosis and modulation of autophagy. Antioxid Redox Signal, 2015, 22(8): 633-650.
21. Cui Changmeng, Cui Jianzhong, Jin Feng, et al. Induction of the vitamin D receptor attenuates autophagy dysfunction-mediated cell death following traumatic brain injury. Cell Physiol Biochem, 2017, 42(5): 1888-1896.
22. Sun Jun. VDR/vitamin D receptor regulates autophagic activity through ATG16L1. Autophagy, 2016, 12(6): 1057-1058.
23. Abdel-Mohsen M A, El-Braky A A, Ghazal A A, et al. Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus. Medicine, 2018, 97(12): e0172.
24. Tavera-Mendoza L E, Westerling T, Libby E, et al. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. Proc Natl Acad Sci USA, 2017, 114(11): E2186-E2194.
25. Seok S, Fu Ting, Choi S E, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature, 2014, 516(7529): 108-111.
26. Lee J M, Wagner M, Xiao Rui, et al. Nutrient-sensing nuclear receptors coordinate autophagy. Nature, 2014, 516(7529): 112-115.
27. Lee J M. Transcriptional coordination of hepatic autophagy by nutrient-sensing nuclear receptor PPARalpha and FXR. Annals of Pediatric Endocrinology Metabolism, 2016, 21(4): 193-198.
28. Zhou Xiaodong, Xie Li, Bergmann F, et al. The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis. Cell Death Discovery, 2017(3): 17027.
29. Sun M M, Beier F, Ratneswaran A. Nuclear receptors as potential drug targets in osteoarthritis. Curr Opin Pharmacol, 2018, 40: 81-86.
30. Zhang Lei, Liu Wen, Wang Qun, et al. New drug candidate targeting the 4A1 orphan nuclear receptor for medullary thyroid cancer therapy. Molecules, 2018, 23(3): 565.

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