B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation

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• 作者：Suji Kim ; Joung-Woo Hong ; Kye Won Park
• 关键词：Btg2 ; Adipocyte differentiation ; Lipid accumulation ; Stat3 ; WP1066
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：413
• 期：1-2
• 页码：145-153
• 全文大小：668 KB
• 参考文献：1.Winkler GS (2010) The mammalian anti-proliferative BTG/Tob protein family. J Cell Physiol 222:66–72CrossRef PubMed
  2.Bradbury A, Possenti R, Shooter EM, Tirone F (1991) Molecular cloning of PC3, a putatively secreted protein whose mRNA is induced by nerve growth factor and depolarization. Proc Natl Acad Sci USA 88:3353–3357PubMedCentral CrossRef PubMed
  3.Fletcher BS, Lim RW, Varnum BC, Kujubu DA, Koski RA, Herschman HR (1991) Structure and expression of TIS21, a primary response gene induced by growth factors and tumor promoters. J Biol Chem 266:14511–14518PubMed
  4.Matsuda S, Rouault J, Magaud J, Berthet C (2001) In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett 497:67–72CrossRef PubMed
  5.Tirone F (2001) The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? J Cell Physiol 187:155–165CrossRef PubMed
  6.Canzoniere D, Farioli-Vecchioli S, Conti F, Ciotti MT, Tata AM, Augusti-Tocco G, Mattei E, Lakshmana MK, Krizhanovsky V, Reeves SA, Giovannoni R, Castano F, Servadio A, Ben-Arie N, Tirone F (2004) Dual control of neurogenesis by PC3 through cell cycle inhibition and induction of Math1. J Neurosci 24:3355–3369CrossRef PubMed
  7.Farioli-Vecchioli S, Saraulli D, Costanzi M, Leonardi L, Cina I, Micheli L, Nutini M, Longone P, Oh SP, Cestari V, Tirone F (2009) Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice. PLoS One 4:e8339PubMedCentral CrossRef PubMed
  8.Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F (2007) Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3. FASEB J 21:2215–2225CrossRef PubMed
  9.Boiko AD, Porteous S, Razorenova OV, Krivokrysenko VI, Williams BR, Gudkov AV (2006) A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Genes Dev 20:236–252PubMedCentral CrossRef PubMed
  10.Ficazzola MA, Fraiman M, Gitlin J, Woo K, Melamed J, Rubin MA, Walden PD (2001) Antiproliferative B cell translocation gene 2 protein is down-regulated post-transcriptionally as an early event in prostate carcinogenesis. Carcinogenesis 22:1271–1279CrossRef PubMed
  11.Struckmann K, Schraml P, Simon R, Elmenhorst K, Mirlacher M, Kononen J, Moch H (2004) Impaired expression of the cell cycle regulator BTG2 is common in clear cell renal cell carcinoma. Cancer Res 64:1632–1638CrossRef PubMed
  12.Kawakubo H, Brachtel E, Hayashida T, Yeo G, Kish J, Muzikansky A, Walden PD, Maheswaran S (2006) Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Cancer Res 66:7075–7082CrossRef PubMed
  13.Passeri D, Marcucci A, Rizzo G, Billi M, Panigada M, Leonardi L, Tirone F, Grignani F (2006) Btg2 enhances retinoic acid-induced differentiation by modulating histone H4 methylation and acetylation. Mol Cell Biol 26:5023–5032PubMedCentral CrossRef PubMed
  14.MacDougald OA, Lane MD (1995) Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 64:345–373CrossRef PubMed
  15.Wang D, Zhou Y, Lei W, Zhang K, Shi J, Hu Y, Shu G, Song J (2009) Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome-proliferator-activated receptor γ (PPARγ). Biol Cell 102:1–12CrossRef PubMed
  16.Quy LN, Choi YW, Kim YH, Chwae YJ, Park TJ, Lim IK (2013) TIS21(/BTG2/PC3) inhibits interleukin-6 expression via downregulation of STAT3 pathway. Cell Signal 25:2391–2399CrossRef PubMed
  17.Baek K, Park HJ, Hwang HR, Baek JH (2014) Propranolol attenuates calorie restriction- and high calorie diet-induced bone marrow adiposity. BMB Rep 47:587–592PubMedCentral CrossRef PubMed
  18.Lu K, Chen N, Zhou XX, Ge XL, Feng LL, Li PP, Li XY, Geng LY, Wang X (2015) The STAT3 inhibitor WP1066 synergizes with vorinostat to induce apoptosis of mantle cell lymphoma cells. Biochem Biophys Res Commun 464:292–298CrossRef PubMed
  19.Zhou X, Ren Y, Liu A, Jin R, Jiang Q, Huang Y, Kong L, Wang X, Zhang L (2014) WP1066 sensitizes oral squamous cell carcinoma cells to cisplatin by targeting STAT3/miR-21 axis. Sci Rep 4:7461PubMedCentral CrossRef PubMed
  20.Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809PubMed
  21.Zhang K, Guo W, Yang Y, Wu J (2011) JAK2/STAT3 pathway is involved in the early stage of adipogenesis through regulating C/EBPbeta transcription. J Cell Biochem 112:488–497CrossRef PubMed
  22.Mikkelsen TS, Xu Z, Zhang X, Wang L, Gimble JM, Lander ES, Rosen ED (2010) Comparative epigenomic analysis of murine and human adipogenesis. Cell 143:156–169PubMedCentral CrossRef PubMed
  23.Cristancho AG, Lazar MA (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12:722–734CrossRef PubMed
  24.Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM (1999) Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 3:151–158CrossRef PubMed
  25.Tang QQ, Zhang JW, Daniel Lane M (2004) Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis. Biochem Biophys Res Commun 319:235–239CrossRef PubMed
  26.Steger DJ, Grant GR, Schupp M, Tomaru T, Lefterova MI, Schug J, Manduchi E, Stoeckert CJ Jr, Lazar MA (2010) Propagation of adipogenic signals through an epigenomic transition state. Genes Dev 24:1035–1044PubMedCentral CrossRef PubMed
  27.Schupp M, Cristancho AG, Lefterova MI, Hanniman EA, Briggs ER, Steger DJ, Qatanani M, Curtin JC, Schug J, Ochsner SA, McKenna NJ, Lazar MA (2009) Re-expression of GATA2 cooperates with peroxisome proliferator-activated receptor-gamma depletion to revert the adipocyte phenotype. J Biol Chem 284:9458–9464PubMedCentral CrossRef PubMed
  28.Deng J, Hua K, Lesser SS, Harp JB (2000) Activation of signal transducer and activator of transcription-3 during proliferative phases of 3T3-L1 adipogenesis. Endocrinology 141:2370–2376PubMed
  29.Stephens JM, Morrison RF, Pilch PF (1996) The expression and regulation of STATs during 3T3-L1 adipocyte differentiation. J Biol Chem 271:10441–10444CrossRef PubMed
  
• 作者单位：Suji Kim (1)
  Joung-Woo Hong (2)
  Kye Won Park (1)
  
  1. Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Korea
  2. Graduate School of East-West Medical Science, Kyung Hee University, Yongin, 17104, Korea
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

Btg2, a member of a family of antiproliferative proteins, is involved in downregulation of the JAK2–Stat3 signaling pathway. Here, we present evidence that the inhibitory effect of Btg2 on adipogenesis is suppressed by the proadipogenic activity of the Stat3 signaling pathway. Btg2 expression fluctuates during adipogenic differentiation of preadipocytes. Btg2 is also expressed at different levels in fat tissues from lean and obese mice. Furthermore, knockdown of Btg2 expression enhanced lipid accumulation and upregulated the expression of adipogenic marker genes. To gain insights into the molecular mechanisms of Btg2 action in adipocytes, adipocytes were treated with previously identified bioactive compounds and the expression of Btg2 was assessed. This effort identified the small molecule WP1066, a known Stat3 inhibitor, as an inducer of Btg2 expression. In line with this observation, siRNA-mediated silencing of Stat3 resulted in upregulated Btg2 expression and decreased lipid accumulation. Furthermore, siRNA-mediated silencing of Btg2 attenuated WP1066-mediated inhibition of adipocyte differentiation. We discuss a model for the role of Btg2 in adipogenesis and propose that Btg2 and Stat3 act in a functional hierarchy. Keywords Btg2 Adipocyte differentiation Lipid accumulation Stat3 WP1066