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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

SRC-3/AIB-1 may Enhance Hepatic NFATC1 Transcription and Mediate Inflammation in a Tissue-Specific Manner in Morbid Obesity

Author(s): Athina Chasapi*, Konstantinos Balampanis, Anna Tanoglidi, Eleni Kourea, George I. Lambrou, Vaia Lambadiari, Fotios Kalfarentzos, Erifili Hatziagelaki, Maria Melachrinou and Georgia Sotiropoulou-Bonikou

Volume 20, Issue 2, 2020

Page: [242 - 255] Pages: 14

DOI: 10.2174/1871530319666190715160630

Price: $65

Abstract

Background: Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders.

Methods: 50 morbidly obese patients participated in the present study. Biopsies were collected from visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, extra-myocellular adipose tissue and liver. We evaluated the differential protein expression of NFATc1, SRC-2/TIF-2, SRC-3/AIB-1 and inflammatory biomarkers CD68 and CD3 by immunohistochemistry. The current study was designed to determine any correlations between the transcription factor NFATc1 and the SRC coregulators, as well as any associations with the inflammatory biomarkers.

Results: We identified SRC-3 as a hepatic NFATc1 coactivator and we demonstrated its possible role in energy homeostasis and lipid metabolism. Moreover, we revealed a complex and extensive intraand inter-tissue network among the three main investigated proteins and the inflammatory biomarkers, suggesting their potential participation in the obesity-induced inflammatory cascade.

Conclusion: Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead to numerous cardiometabolic diseases. Further on, our present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.

Keywords: Obesity, diabetes, NFATc1, SRC-3/AIB-1, Inflammation, Liver (Hepar), metabolic syndrome.

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[1]
Friedrich, M.J. Global obesity epidemic worsening. JAMA, 2017, 318(7), 603.
[PMID: 28810033]
[2]
Barabási, A.L. Network medicine--from obesity to the “diseasome”. N. Engl. J. Med., 2007, 357(4), 404-407.
[http://dx.doi.org/10.1056/NEJMe078114] [PMID: 17652657]
[3]
Hruby, A.; Hu, F.B. The epidemiology of obesity: A big picture. Pharmacoeconomics, 2015, 33(7), 673-689.
[http://dx.doi.org/10.1007/s40273-014-0243-x] [PMID: 25471927]
[4]
Musso, G.; Gambino, R.; Bo, S.; Uberti, B.; Biroli, G.; Pagano, G.; Cassader, M. Should nonalcoholic fatty liver disease be included in the definition of metabolic syndrome? A cross-sectional comparison with Adult Treatment Panel III criteria in nonobese nondiabetic subjects. Diabetes Care, 2008, 31(3), 562-568.
[http://dx.doi.org/10.2337/dc07-1526] [PMID: 18056890]
[5]
Fabbrini, E.; Sullivan, S.; Klein, S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology, 2010, 51(2), 679-689.
[http://dx.doi.org/10.1002/hep.23280] [PMID: 20041406]
[6]
Monteiro, J.M.; Monteiro, G.M.; Caroli-Bottino, A.; Pannain, V.L. Nonalcoholic fatty liver disease: different classifications concordance and relationship between degrees of morphological features and spectrum of the disease. Anal. Cell. Pathol. (Amst.), 2014.2014526979
[http://dx.doi.org/10.1155/2014/526979] [PMID: 25763333]
[7]
Feige, J.N.; Auwerx, J. Transcriptional coregulators in the control of energy homeostasis. Trends Cell Biol., 2007, 17(6), 292-301.
[http://dx.doi.org/10.1016/j.tcb.2007.04.001] [PMID: 17475497]
[8]
Martinez, G.J.; Pereira, R.M.; Äijö, T.; Kim, E.Y.; Marangoni, F.; Pipkin, M.E.; Togher, S.; Heissmeyer, V.; Zhang, Y.C.; Crotty, S.; Lamperti, E.D.; Ansel, K.M.; Mempel, T.R.; Lähdesmäki, H.; Hogan, P.G.; Rao, A. The transcription factor NFAT promotes exhaustion of activated CD8+ T cells. Immunity, 2015, 42(2), 265-278.
[http://dx.doi.org/10.1016/j.immuni.2015.01.006] [PMID: 25680272]
[9]
Stieger, P.; Braun-Dullaeus, R.C. The dissimilar siblings or: the NFAT-modulated yin and yang of AIF-1 and IRT-1 in cardiovascular diseases. Cardiovasc. Res., 2012, 93(3), 388-389.
[http://dx.doi.org/10.1093/cvr/cvs023] [PMID: 22271706]
[10]
Yang, T.T.; Suk, H.Y.; Yang, X.; Olabisi, O.; Yu, R.Y.; Durand, J.; Jelicks, L.A.; Kim, J.Y.; Scherer, P.E.; Wang, Y.; Feng, Y.; Rossetti, L.; Graef, I.A.; Crabtree, G.R.; Chow, C.W. Role of transcription factor NFAT in glucose and insulin homeostasis. Mol. Cell. Biol., 2006, 26(20), 7372-7387.
[http://dx.doi.org/10.1128/MCB.00580-06] [PMID: 16908540]
[11]
Smith, C.L.; O’Malley, B.W. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev., 2004, 25(1), 45-71.
[http://dx.doi.org/10.1210/er.2003-0023] [PMID: 14769827]
[12]
Dasgupta, S.; O’Malley, B.W. Transcriptional coregulators: emerging roles of SRC family of coactivators in disease pathology. J. Mol. Endocrinol., 2014, 53(2), R47-R59.
[http://dx.doi.org/10.1530/JME-14-0080] [PMID: 25024406]
[13]
Spiegelman, B.M.; Heinrich, R. Biological control through regulated transcriptional coactivators. Cell, 2004, 119(2), 157-167.
[http://dx.doi.org/10.1016/j.cell.2004.09.037] [PMID: 15479634]
[14]
Lonard, D.M.; O’malley, B.W. Nuclear receptor coregulators: judges, juries, and executioners of cellular regulation. Mol. Cell, 2007, 27(5), 691-700.
[http://dx.doi.org/10.1016/j.molcel.2007.08.012] [PMID: 17803935]
[15]
York, B.; O’Malley, B.W. Steroid receptor coactivator (SRC) family: masters of systems biology. J. Biol. Chem., 2010, 285(50), 38743-38750.
[http://dx.doi.org/10.1074/jbc.R110.193367] [PMID: 20956538]
[16]
Picard, F.; Géhin, M.; Annicotte, J.; Rocchi, S.; Champy, M.F.; O’Malley, B.W.; Chambon, P.; Auwerx, J. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell, 2002, 111(7), 931-941.
[http://dx.doi.org/10.1016/S0092-8674(02)01169-8] [PMID: 12507421]
[17]
Coste, A.; Antal, M.C.; Chan, S.; Kastner, P.; Mark, M.; O’Malley, B.W.; Auwerx, J. Absence of the steroid receptor coactivator-3 induces B-cell lymphoma. EMBO J., 2006, 25(11), 2453-2464.
[http://dx.doi.org/10.1038/sj.emboj.7601106] [PMID: 16675958]
[18]
Grivas, P.D.; Tzelepi, V.; Sotiropoulou-Bonikou, G.; Kefalopoulou, Z.; Papavassiliou, A.G.; Kalofonos, H. Estrogen receptor alpha/beta, AIB1, and TIF2 in colorectal carcinogenesis: do coregulators have prognostic significance? Int. J. Colorectal Dis., 2009, 24(6), 613-622.
[http://dx.doi.org/10.1007/s00384-009-0647-9] [PMID: 19198856]
[19]
Tzelepi, V.; Grivas, P.; Kefalopoulou, Z.; Kalofonos, H.; Varakis, J.N.; Melachrinou, M.; Sotiropoulou-Bonikou, G. Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression. Virchows Arch., 2009, 454(4), 389-399.
[http://dx.doi.org/10.1007/s00428-009-0740-z] [PMID: 19277704]
[20]
Kefalopoulou, Z.; Tzelepi, V.; Zolota, V.; Grivas, P.D.; Christopoulos, C.; Kalofonos, H.; Maraziotis, T.; Sotiropoulou-Bonikou, G. Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and worse patient prognosis. J. Neurooncol., 2012, 106(1), 23-31.
[http://dx.doi.org/10.1007/s11060-011-0637-y] [PMID: 21735116]
[21]
Tien, J.C.; Xu, J. Steroid receptor coactivator-3 as a potential molecular target for cancer therapy. Expert Opin. Ther. Targets, 2012, 16(11), 1085-1096.
[http://dx.doi.org/10.1517/14728222.2012.718330] [PMID: 22924430]
[22]
Louet, J.F.; Coste, A.; Amazit, L.; Tannour-Louet, M.; Wu, R.C.; Tsai, S.Y.; Tsai, M.J.; Auwerx, J.; O’Malley, B.W. Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program. Proc. Natl. Acad. Sci. USA, 2006, 103(47), 17868-17873.
[http://dx.doi.org/10.1073/pnas.0608711103] [PMID: 17098861]
[23]
Malovannaya, A.; Li, Y.; Bulynko, Y.; Jung, S.Y.; Wang, Y.; Lanz, R.B.; O’Malley, B.W.; Qin, J. Streamlined analysis schema for high-throughput identification of endogenous protein complexes. Proc. Natl. Acad. Sci. USA, 2010, 107(6), 2431-2436.
[http://dx.doi.org/10.1073/pnas.0912599106] [PMID: 20133760]
[24]
Feng, Q.; O’Malley, B.W. Nuclear receptor modulation--role of coregulators in selective estrogen receptor modulator (SERM) actions. Steroids, 2014, 90, 39-43.
[http://dx.doi.org/10.1016/j.steroids.2014.06.008] [PMID: 24945111]
[25]
Balampanis, K.; Chasapi, A.; Kourea, E.; Tanoglidi, A.; Hatziagelaki, E.; Lambadiari, V.; Dimitriadis, G.; Lambrou, G.I.; Kalfarentzos, F.; Melachrinou, M.; Sotiropoulou-Bonikou, G. Intertissue expression patterns of the key metabolic biomarker PGC-1α in severely obese individuals: Implication in obesity-induced disease. Hellenic J. Cardiol, 2018, S1109-9666(18)30252-5.
[http://dx.doi.org/10.1016/j.hjc.2018.08.002] [PMID: 30138744]
[26]
Chasapi, A.; Balampanis, K.; Kourea, E.; Kalfarentzos, F.; Lambadiari, V.; Lambrou, G.I.; Melachrinou, M.; Sotiropoulou-Bonikou, G. Can obesity-induced inflammation in skeletal muscle and intramuscular adipose tissue accurately detect liver fibrosis? J. Musculoskelet. Neuronal Interact., 2018, 18(4), 509-524.
[PMID: 30511955]
[27]
Addison, O.; Marcus, R.L.; Lastayo, P.C.; Ryan, A.S. Intermuscular fat: a review of the consequences and causes. Int. J. Endocrinol., 2014. 2014309570
[http://dx.doi.org/10.1155/2014/309570] [PMID: 24527032]
[28]
Khan, I.M.; Perrard, X.Y.; Brunner, G.; Lui, H.; Sparks, L.M.; Smith, S.R.; Wang, X.; Shi, Z.Z.; Lewis, D.E.; Wu, H.; Ballantyne, C.M. Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltration and insulin resistance. Int. J. Obes., 2015, 39(11), 1607-1618.
[http://dx.doi.org/10.1038/ijo.2015.104] [PMID: 26041698]
[29]
Kleiner, D.E.; Brunt, E.M.; Van Natta, M.; Behling, C.; Contos, M.J.; Cummings, O.W.; Ferrell, L.D.; Liu, Y.C.; Torbenson, M.S.; Unalp-Arida, A.; Yeh, M.; McCullough, A.J.; Sanyal, A.J. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 2005, 41(6), 1313-1321.
[http://dx.doi.org/10.1002/hep.20701] [PMID: 15915461]
[30]
Mackey, A.L.; Brandstetter, S.; Schjerling, P.; Bojsen-Moller, J.; Qvortrup, K.; Pedersen, M.M.; Doessing, S.; Kjaer, M.; Magnusson, S.P.; Langberg, H. Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle. FASEB J., 2011, 25(6), 1943-1959.
[http://dx.doi.org/10.1096/fj.10-176487] [PMID: 21368102]
[31]
Roche, J.A.; Lovering, R.M.; Roche, R.; Ru, L.W.; Reed, P.W.; Bloch, R.J. Extensive mononuclear infiltration and myogenesis characterize recovery of dysferlin-null skeletal muscle from contraction-induced injuries. Am. J. Physiol. Cell Physiol., 2010, 298(2), C298-C312.
[http://dx.doi.org/10.1152/ajpcell.00122.2009] [PMID: 19923419]
[32]
Wanschitz, J.V.; Dubourg, O.; Lacene, E.; Fischer, M.B.; Höftberger, R.; Budka, H.; Romero, N.B.; Eymard, B.; Herson, S.; Butler-Browne, G.S.; Voit, T.; Benveniste, O. Expression of myogenic regulatory factors and myo-endothelial remodeling in sporadic inclusion body myositis. Neuromuscul. Disord., 2013, 23(1), 75-83.
[http://dx.doi.org/10.1016/j.nmd.2012.09.003] [PMID: 23058947]
[33]
Bigornia, S.J.; Farb, M.G.; Mott, M.M.; Hess, D.T.; Carmine, B.; Fiscale, A.; Joseph, L.; Apovian, C.M.; Gokce, N. Relation of depot- specific adipose inflammation to insulin resistance in human obesity. Nutr. Diabetes, 2012, 2, e30.
[http://dx.doi.org/10.1038/nutd.2012.3] [PMID: 23449529]
[34]
Grivas, P.D.; Tzelepi, V.; Sotiropoulou-Bonikou, G.; Kefalopoulou, Z.; Papavassiliou, A.G.; Kalofonos, H. Expression of ERalpha, ERbeta and co-regulator PELP1/MNAR in colorectal cancer: prognostic significance and clinicopathologic correlations. Cell. Oncol., 2009, 31(3), 235-247.
[PMID: 19478391]
[35]
Lin, J.; Handschin, C.; Spiegelman, B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab., 2005, 1(6), 361-370.
[http://dx.doi.org/10.1016/j.cmet.2005.05.004] [PMID: 16054085]
[36]
Lerin, C.; Rodgers, J.T.; Kalume, D.E.; Kim, S.H.; Pandey, A.; Puigserver, P. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab., 2006, 3(6), 429-438.
[http://dx.doi.org/10.1016/j.cmet.2006.04.013] [PMID: 16753578]
[37]
Reineke, E.L.; York, B.; Stashi, E.; Chen, X.; Tsimelzon, A.; Xu, J.; Newgard, C.B.; Taffet, G.E.; Taegtmeyer, H.; Entman, M.L.; O’Malley, B.W. SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart. PLoS One, 2012, 7(12)e53395
[http://dx.doi.org/10.1371/journal.pone.0053395] [PMID: 23300926]
[38]
Chopra, A.R.; Louet, J.F.; Saha, P.; An, J.; Demayo, F.; Xu, J.; York, B.; Karpen, S.; Finegold, M.; Moore, D.; Chan, L.; Newgard, C.B.; O’Malley, B.W. Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke’s disease. Science, 2008, 322(5906), 1395-1399.
[http://dx.doi.org/10.1126/science.1164847] [PMID: 19039140]
[39]
Chopra, A.R.; Kommagani, R.; Saha, P.; Louet, J.F.; Salazar, C.; Song, J.; Jeong, J.; Finegold, M.; Viollet, B.; DeMayo, F.; Chan, L.; Moore, D.D.; O’Malley, B.W. Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption. Cell Metab., 2011, 13(1), 35-43.
[http://dx.doi.org/10.1016/j.cmet.2010.12.001] [PMID: 21195347]
[40]
Dasgupta, S.; Putluri, N.; Long, W.; Zhang, B.; Wang, J.; Kaushik, A.K.; Arnold, J.M.; Bhowmik, S.K.; Stashi, E.; Brennan, C.A.; Rajapakshe, K.; Coarfa, C.; Mitsiades, N.; Ittmann, M.M.; Chinnaiyan, A.M.; Sreekumar, A.; O’Malley, B.W. Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis. J. Clin. Invest., 2015, 125(3), 1174-1188.
[http://dx.doi.org/10.1172/JCI76029] [PMID: 25664849]
[41]
Stashi, E.; Lanz, R.B.; Mao, J.; Michailidis, G.; Zhu, B.; Kettner, N.M.; Putluri, N.; Reineke, E.L.; Reineke, L.C.; Dasgupta, S.; Dean, A.; Stevenson, C.R.; Sivasubramanian, N.; Sreekumar, A.; Demayo, F.; York, B.; Fu, L.; O’Malley, B.W. SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell Rep., 2014, 6(4), 633-645.
[http://dx.doi.org/10.1016/j.celrep.2014.01.027] [PMID: 24529706]
[42]
York, B.; Reineke, E.L.; Sagen, J.V.; Nikolai, B.C.; Zhou, S.; Louet, J.F.; Chopra, A.R.; Chen, X.; Reed, G.; Noebels, J.; Adesina, A.M.; Yu, H.; Wong, L.J.; Tsimelzon, A.; Hilsenbeck, S.; Stevens, R.D.; Wenner, B.R.; Ilkayeva, O.; Xu, J.; Newgard, C.B.; O’Malley, B.W. Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy. Cell Metab., 2012, 15(5), 752-763.
[http://dx.doi.org/10.1016/j.cmet.2012.03.020] [PMID: 22560224]
[43]
Louet, J.F.; O’Malley, B.W. Coregulators in adipogenesis: what could we learn from the SRC (p160) coactivator family? Cell Cycle, 2007, 6(20), 2448-2452.
[http://dx.doi.org/10.4161/cc.6.20.4777] [PMID: 17704643]
[44]
Ma, X.; Xu, L.; Wang, S.; Cui, B.; Li, X.; Xu, J.; Ning, G. Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis. J. Hepatol., 2011, 55(2), 445-452.
[http://dx.doi.org/10.1016/j.jhep.2010.11.022] [PMID: 21184786]
[45]
Ma, X.; Xu, L.; Wang, S.; Chen, H.; Xu, J.; Li, X.; Ning, G. Loss of steroid receptor co-activator-3 attenuates carbon tetrachloride-induced murine hepatic injury and fibrosis. Lab. Invest., 2009, 89(8), 903-914.
[http://dx.doi.org/10.1038/labinvest.2009.51] [PMID: 19488034]
[46]
Liu, Y.; Tong, Z.; Li, T.; Chen, Q.; Zhuo, L.; Li, W.; Wu, R.C.; Yu, C. Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness. Hepatology, 2012, 56(3), 1015-1024.
[http://dx.doi.org/10.1002/hep.25751] [PMID: 22473901]
[47]
Zhang, H.; Xie, X.; Zhu, X.; Zhu, J.; Hao, C.; Lu, Q.; Ding, L.; Liu, Y.; Zhou, L.; Liu, Y.; Huang, C.; Wen, C.; Ye, Q. Stimulatory cross-talk between NFAT3 and estrogen receptor in breast cancer cells. J. Biol. Chem., 2005, 280(52), 43188-43197.
[http://dx.doi.org/10.1074/jbc.M506598200] [PMID: 16219765]
[48]
Littman, D.R.; Sun, Z.; Unutmaz, D.; Sunshine, M.J.; Petrie, H.T.; Zou, Y.R. Role of the nuclear hormone receptor ROR gamma in transcriptional regulation, thymocyte survival, and lymphoid organogenesis. Cold Spring Harb. Symp. Quant. Biol., 1999, 64, 373-381.
[http://dx.doi.org/10.1101/sqb.1999.64.373] [PMID: 11232310]
[49]
Xie, H.; Sadim, M.S.; Sun, Z. RORgammat recruits steroid receptor coactivators to ensure thymocyte survival. J. Immunol., 2005, 175(6), 3800-3809.
[http://dx.doi.org/10.4049/jimmunol.175.6.3800] [PMID: 16148126]
[50]
Fric, J.; Zelante, T.; Wong, A.Y.; Mertes, A.; Yu, H.B.; Ricciardi-Castagnoli, P. NFAT control of innate immunity. Blood, 2012, 120(7), 1380-1389.
[http://dx.doi.org/10.1182/blood-2012-02-404475] [PMID: 22611159]
[51]
Pan, M.G.; Xiong, Y.; Chen, F. NFAT gene family in inflammation and cancer. Curr. Mol. Med., 2013, 13(4), 543-554.
[http://dx.doi.org/10.2174/1566524011313040007] [PMID: 22950383]
[52]
Yarilina, A.; Xu, K.; Chen, J.; Ivashkiv, L.B. TNF activates calcium-nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages. Proc. Natl. Acad. Sci. USA, 2011, 108(4), 1573-1578.
[http://dx.doi.org/10.1073/pnas.1010030108] [PMID: 21220349]
[53]
Pan, M.; Winslow, M.M.; Chen, L.; Kuo, A.; Felsher, D.; Crabtree, G.R. Enhanced NFATc1 nuclear occupancy causes T cell activation independent of CD28 costimulation. J. Immunol., 2007, 178(7), 4315-4321.
[http://dx.doi.org/10.4049/jimmunol.178.7.4315] [PMID: 17371988]
[54]
Buchholz, M.; Schatz, A.; Wagner, M.; Michl, P.; Linhart, T.; Adler, G.; Gress, T.M.; Ellenrieder, V. Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway. EMBO J., 2006, 25(15), 3714-3724.
[http://dx.doi.org/10.1038/sj.emboj.7601246] [PMID: 16874304]
[55]
Singh, G.; Singh, S.K.; König, A.; Reutlinger, K.; Nye, M.D.; Adhikary, T.; Eilers, M.; Gress, T.M.; Fernandez-Zapico, M.E.; Ellenrieder, V. Sequential activation of NFAT and c-Myc transcription factors mediates the TGF-beta switch from a suppressor to a promoter of cancer cell proliferation. J. Biol. Chem., 2010, 285(35), 27241-27250.
[http://dx.doi.org/10.1074/jbc.M110.100438] [PMID: 20516082]
[56]
Robbs, B.K.; Cruz, A.L.; Werneck, M.B.; Mognol, G.P.; Viola, J.P. Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors. Mol. Cell. Biol., 2008, 28(23), 7168-7181.
[http://dx.doi.org/10.1128/MCB.00256-08] [PMID: 18809576]
[57]
Yu, C.; York, B.; Wang, S.; Feng, Q.; Xu, J.; O’Malley, B.W. An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. Mol. Cell, 2007, 25(5), 765-778.
[http://dx.doi.org/10.1016/j.molcel.2007.01.025] [PMID: 17349961]
[58]
Li, J.; Liu, Y.H.; Ou, S.; Dai, X.M.; Wang, J.P.; Su, Y.P. Steroid receptor coactivator-3 differentially regulates the inflammatory response in peritoneal macrophages. Mol. Med. Rep., 2012, 5(4), 1099-1105.
[http://dx.doi.org/10.3892/mmr.2012.750] [PMID: 22245955]
[59]
Werbajh, S.; Nojek, I.; Lanz, R.; Costas, M.A. RAC-3 is a NF-kappa B coactivator. FEBS Lett., 2000, 485(2-3), 195-199.
[http://dx.doi.org/10.1016/S0014-5793(00)02223-7] [PMID: 11094166]
[60]
Wu, R.C.; Qin, J.; Hashimoto, Y.; Wong, J.; Xu, J.; Tsai, S.Y.; Tsai, M.J.; O’Malley, B.W. Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol. Cell. Biol., 2002, 22(10), 3549-3561.
[http://dx.doi.org/10.1128/MCB.22.10.3549-3561.2002] [PMID: 11971985]
[61]
Song, X.; Chen, J.; Zhao, M.; Zhang, C.; Yu, Y.; Lonard, D.M.; Chow, D.C.; Palzkill, T.; Xu, J.; O’Malley, B.W.; Wang, J. Development of potent small-molecule inhibitors to drug the undruggable steroid receptor coactivator-3. Proc. Natl. Acad. Sci. USA, 2016, 113(18), 4970-4975.
[http://dx.doi.org/10.1073/pnas.1604274113] [PMID: 27084884]
[62]
Wang, Y.; Lonard, D.M.; Yu, Y.; Chow, D.C.; Palzkill, T.G.; Wang, J.; Qi, R.; Matzuk, A.J.; Song, X.; Madoux, F.; Hodder, P.; Chase, P.; Griffin, P.R.; Zhou, S.; Liao, L.; Xu, J.; O’Malley, B.W. Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. Cancer Res., 2014, 74(5), 1506-1517.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-2939] [PMID: 24390736]
[63]
Wang, Y.; Lonard, D.M.; Yu, Y.; Chow, D.C.; Palzkill, T.G.; O’Malley, B.W. Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. Mol. Endocrinol., 2011, 25(12), 2041-2053.
[http://dx.doi.org/10.1210/me.2011-1222] [PMID: 22053001]
[64]
Mao, I.; Liu, J.; Li, X.; Luo, H. REGgamma, a proteasome activator and beyond? Cell. Mol. Life Sci., 2008, 65(24), 3971-3980.
[http://dx.doi.org/10.1007/s00018-008-8291-z] [PMID: 18679578]
[65]
Ayala, G.; Yan, J.; Li, R.; Ding, Y.; Thompson, T.C.; Mims, M.P.; Hayes, T.G.; MacDonnell, V.; Lynch, R.G.; Frolov, A.; Miles, B.J.; Wheeler, T.M.; Harper, J.W.; Tsai, M.J.; Ittmann, M.M.; Kadmon, D. Bortezomib-mediated inhibition of steroid receptor coactivator-3 degradation leads to activated Akt. Clin. Cancer Res., 2008, 14(22), 7511-7518.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0839] [PMID: 19010869]
[66]
Louie, M.C.; Revenko, A.S.; Zou, J.X.; Yao, J.; Chen, H.W. Direct control of cell cycle gene expression by proto-oncogene product ACTR, and its autoregulation underlies its transforming activity. Mol. Cell. Biol., 2006, 26(10), 3810-3823.
[http://dx.doi.org/10.1128/MCB.26.10.3810-3823.2006] [PMID: 16648476]
[67]
Zhou, G.; Hashimoto, Y.; Kwak, I.; Tsai, S.Y.; Tsai, M.J. Role of the steroid receptor coactivator SRC-3 in cell growth. Mol. Cell. Biol., 2003, 23(21), 7742-7755.
[http://dx.doi.org/10.1128/MCB.23.21.7742-7755.2003] [PMID: 14560019]

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