DOI QR코드

DOI QR Code

HCBP6 upregulates human SREBP1c expression by binding to C/EBPβ-binding site in the SREBP1c promoter

  • Yang, Xueliang (Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University) ;
  • Han, Ming (Peking University Ditan Teaching Hospital) ;
  • Liu, Shunai (Beijing Key Laboratory of Emerging Infectious Diseases) ;
  • Yuan, Xiaoxue (Beijing Key Laboratory of Emerging Infectious Diseases) ;
  • Liu, Xiaojing (Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University) ;
  • Feng, Shenghu (Peking University Ditan Teaching Hospital) ;
  • Zhou, Li (Peking University Ditan Teaching Hospital) ;
  • Li, Yaru (Beijing Key Laboratory of Emerging Infectious Diseases) ;
  • Lu, Hongping (Beijing Key Laboratory of Emerging Infectious Diseases) ;
  • Cheng, Jun (Peking University Ditan Teaching Hospital) ;
  • Lin, Shumei (Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University)
  • Received : 2017.09.12
  • Accepted : 2017.11.20
  • Published : 2018.01.31

Abstract

Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased intracellular TG levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription by directly binding to the SREBP1c promoter (at the -139- to +359-bp region). Moreover, we observed that HCBP6 interacted with $C/EBP{\beta}-binding$ site in the SREBP1c promoter both in vitro and in vivo. These results indicate that HCBP6 upregulates human SREBP1c expression by binding to the $C/EBP{\beta}-binding$ site in the SREBP1c promoter.

Keywords

References

  1. Tilg H, Moschen AR and Roden M (2017) NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol 1, 32-42
  2. Jin J, Iakova P, Breaux M et al (2013) Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis. Cell Rep 3, 831-843 https://doi.org/10.1016/j.celrep.2013.02.009
  3. Farrell GC, Wong VW and Chitturi S (2013) NAFLD in Asia--as common and important as in the West. Nat Rev Gastroenterol Hepatol 5, 307-318
  4. Hua X, Sakai J, Ho YK, Goldstein JL and Brown MS (1995) Hairpin orientation of sterol regulatory element-binding protein-2 in cell membranes as determined by protease protection. J Biol Chem 49, 29422-29427
  5. Lee SJ, Sekimoto T, Yamashita E et al (2003) The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science (New York, NY) 5650, 1571-1575
  6. Eberle D, Hegarty B, Bossard P, Ferre P and Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 11, 839-848
  7. Zhang X, Liu J, Su W et al (2014) Liver X receptor activation increases hepatic fatty acid desaturation by the induction of SCD1 expression through an LXRalpha-SREBP1c-dependent mechanism. J Diabetes 3, 212-220
  8. Liu L, Zhao X, Zhao L et al (2016) Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth. Cancer Res 5, 1260-1272
  9. Park SH, Kim J, Yu M, Park JH, Kim YS and Moon Y (2016) Epithelial Cholesterol Deficiency Attenuates Human Antigen R-linked Pro-inflammatory Stimulation via an SREBP2-linked Circuit. J Biol Chem 47, 24641-24656
  10. Deng X, Cagen LM, Wilcox HG, Park EA, Raghow R and Elam MB (2002) Regulation of the rat SREBP-1c promoter in primary rat hepatocytes. Biochem Biophys Res Commun 1, 256-262
  11. Cagen LM, Deng X, Wilcox HG, Park EA, Raghow R and Elam MB (2005) Insulin activates the rat sterol-regulatoryelement-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements. Biochem J Pt 1, 207-216
  12. Payne Victoria A, Au W-S, Lowe Christopher E et al (2010) C/EBP transcription factors regulateSREBP1cgene expression during adipogenesis. Biochem J 1, 215-224
  13. Li K, Wang L, Cheng J et al (2002) [Screening and cloning gene of hepatocyte protein interacting with hepatitis C virus core protein]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 16, 351-353
  14. Gao LL, Li M, Wang Q, Liu SA, Zhang JQ and Cheng J (2015) HCBP6 Modulates Triglyceride Homeostasis in Hepatocytes Via the SREBP1c/FASN Pathway. J Cell Biochem 10, 2375-2384
  15. Li K, Wang L, Cheng J et al (2002) Hepatitis C virus protein binding protein. World Chinese J Digestol 2, 215-217
  16. Li Q, Cheng J, Liang Y and Cheng M (2003) Hepatitis C virus infection affects lipid metabolism. World Chinese J Digestol 12, 1951-1954
  17. Cheng J (2002) Correlation between hepatitis C virus infection and lipid metabolism. Chinese Hepatol 1, 56-58
  18. Li M, Wang Q, Liu SA et al (2015) MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein. World J Gastroenterol 15, 4517-4525
  19. Khan M, Jahan S, Khaliq S et al (2010) Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis. Arch Virol 11, 1735-1753
  20. Kim KH, Hong SP, Kim K, Park MJ, Kim KJ and Cheong J (2007) HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARgamma. Biochem Biophys Res Commun 4, 883-888
  21. Yamaguchi A, Tazuma S, Nishioka T et al (2005) Hepatitis C virus core protein modulates fatty acid metabolism and thereby causes lipid accumulation in the liver. Dig Dis Sci 7, 1361-1371
  22. Wang L, Cheng J, Li K and Hong Y (2006) [Identification and evaluation promoter sequence and the transcription activation of Hcbp6 interaction with core protein of hepatitis C virus]. Chinese J Hepatol 2, 81-85
  23. Jang H, Lee GY, Selby CP et al (2016) SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding. Nature Commun 12180
  24. Wang Y, Viscarra J, Kim SJ and Sul HS (2015) Transcriptional regulation of hepatic lipogenesis. Nature Rev Mol Cell Biol 11, 678-689
  25. Deng X, Yellaturu C, Cagen L et al (2007) Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1). J Biol Chem 24, 17517-17529
  26. Dif N, Euthine V, Gonnet E, Laville M, Vidal H and Lefai E (2006) Insulin activates human sterol-regulatory-elementbinding protein-1c (SREBP-1c) promoter through SRE motifs. Biochem J 1, 179-188
  27. Shen L, Cui A, Xue Y et al (2014) Hepatic differentiated embryo-chondrocyte-expressed gene 1 (Dec1) inhibits sterol regulatory element-binding protein-1c (Srebp-1c) expression and alleviates fatty liver phenotype. J Biol Chem 34, 23332-23342
  28. Cheng J (2003) Molecular biological mechanism of hepatitis virus interaction with hepatocytes. Zhong Xi Yi Jie He Gan Bing Za Zhi 6, 3
  29. Cheng J (2006) Study on cloning of new gene related to pathogenesis of chronic hepatitis virus infection. Da Lian Da Xue Xue Bao 4, 4
  30. Tian J, Goldstein JL and Brown MS (2016) Insulin induction of SREBP-1c in rodent liver requires LXRalpha-C/EBPbeta complex. Proc Natl Acad Sci U S A 29, 8182-8187
  31. Schroeder-Gloeckler JM, Rahman SM, Janssen RC et al (2007) CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. J Biol Chem 21, 15717-15729
  32. Rahman SM, Schroeder-Gloeckler JM, Janssen RC et al (2007) CCAAT/enhancing binding protein beta deletion in mice attenuates inflammation, endoplasmic reticulum stress, and lipid accumulation in diet-induced nonalcoholic steatohepatitis. Hepatology 5, 1108-1117
  33. Xi Y, Shen W, Ma L et al (2016) HMGA2 promotes adipogenesis by activating C/EBPbeta-mediated expression of PPARgamma. Biochem Biophys Res Commun 4, 617-623
  34. Chen G, Liang G, Ou J, Goldstein JL and Brown MS (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A 31, 11245-11250