Hnf4a

Summary

Gene Symbol: Hnf4a
Description: hepatocyte nuclear factor 4, alpha
Alias: Hnf4, Hnf4alpha, hepatocyte nuclear factor 4-alpha, HNF-4-alpha, TCF-14, alpha transcription factor 4, hepatic nuclear factor 4, alpha, nuclear receptor subfamily 2 group A member 1, transcription factor 14, transcription factor HNF-4
Species: rat
Products:     Hnf4a

Top Publications

  1. Harries L, Brown J, Gloyn A. Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PLoS ONE. 2009;4:e7855 pubmed publisher
    The HNF1A, HNF1B and HNF4A genes are part of an autoregulatory network in mammalian pancreas, liver, kidney and gut...
  2. Sladek F, Zhong W, Lai E, Darnell J. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990;4:2353-65 pubmed
    ..The similarity between HNF-4 and other ligand-dependent transcription factors raises the possibility that HNF-4 and the genes it regulates respond to an as yet unidentified ligand. ..
  3. Yamagata K, Furuta H, Oda N, Kaisaki P, Menzel S, Cox N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature. 1996;384:458-60 pubmed
    ..Here we show that MODY1 is the gene encoding HNF-4alpha (gene symbol, TCF14), a member of the steroid/thyroid hormone receptor superfamily and an upstream regulator of HNF-1alpha expression. ..
  4. Holmkvist J, Almgren P, Lyssenko V, Lindgren C, Eriksson K, Isomaa B, et al. Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes. 2008;57:1738-44 pubmed publisher
  5. Nyirenda M, Dean S, Lyons V, Chapman K, Seckl J. Prenatal programming of hepatocyte nuclear factor 4alpha in the rat: A key mechanism in the 'foetal origins of hyperglycaemia'?. Diabetologia. 2006;49:1412-20 pubmed
    ..used to measure and localise hepatic mRNA transcribed from the genes for PCK2, hepatocyte nuclear factor 4, alpha (HNF4A), transcription factor 1 (TCF1), CCAAT/enhancer binding protein, alpha (CEBPA), CEBPB, the glucocorticoid receptor ..
  6. Niehof M, Borlak J. HNF4 alpha and the Ca-channel TRPC1 are novel disease candidate genes in diabetic nephropathy. Diabetes. 2008;57:1069-77 pubmed publisher
    The nuclear receptor hepatic nuclear factor 4 alpha (HNF 4 alpha) is a master regulatory protein and an essential player in the control of a wide range of metabolic processes...
  7. Hayhurst G, Lee Y, Lambert G, Ward J, Gonzalez F. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 2001;21:1393-403 pubmed
    ..Of these, only HNF4alpha (nuclear receptor 2A1) and HNF1alpha appear to be correlated with the differentiated phenotype of cultured ..
  8. Gupta R, Vatamaniuk M, Lee C, Flaschen R, Fulmer J, Matschinsky F, et al. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J Clin Invest. 2005;115:1006-15 pubmed
    ..Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel. ..
  9. Nakhei H, Lingott A, Lemm I, Ryffel G. An alternative splice variant of the tissue specific transcription factor HNF4alpha predominates in undifferentiated murine cell types. Nucleic Acids Res. 1998;26:497-504 pubmed
    The transcription factor hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue specific transcription factor mainly expressed in the liver, kidney, intestine and the endocrine pancreas, but is also an essential regulator for early ..

More Information

Publications62

  1. Kapoor R, Locke J, Colclough K, Wales J, Conn J, Hattersley A, et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes. 2008;57:1659-63 pubmed publisher
    Mutations in the human HNF4A gene encoding the hepatocyte nuclear factor (HNF)-4alpha are known to cause maturity-onset diabetes of the young (MODY), which is characterized by autosomal-dominant inheritance and impaired glucose-..
  2. Pearson E, Boj S, Steele A, Barrett T, Stals K, Shield J, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007;4:e118 pubmed
    ..hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4alpha) and HNF1A/TCF1 (encoding HNF-1alpha), and the effect of pancreatic deletion of Hnf4a on ..
  3. Chiba H, Itoh T, Satohisa S, Sakai N, Noguchi H, Osanai M, et al. Activation of p21CIP1/WAF1 gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4alpha. Exp Cell Res. 2005;302:11-21 pubmed
  4. Chiba H, Gotoh T, Kojima T, Satohisa S, Kikuchi K, Osanai M, et al. Hepatocyte nuclear factor (HNF)-4alpha triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells. Exp Cell Res. 2003;286:288-97 pubmed
    ..These findings indicate that HNF-4alpha triggers de novo formation of functional tight junctions and establishment of epithelial cell polarity. ..
  5. Kamiyama Y, Matsubara T, Yoshinari K, Nagata K, Kamimura H, Yamazoe Y. Role of human hepatocyte nuclear factor 4alpha in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet. 2007;22:287-98 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is an important transcription factor in hepatic gene expression...
  6. Yokomori N, Nishio K, Aida K, Negishi M. Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver. J Steroid Biochem Mol Biol. 1997;62:307-14 pubmed
    ..It appears, therefore, that HNF-4 activates the hepatic transcription of Cyp2a-4 gene through its direct binding to the regulatory element regardless of the methylation at position -50. ..
  7. Wiwi C, Waxman D. Role of hepatocyte nuclear factors in growth hormone-regulated, sexually dimorphic expression of liver cytochromes P450. Growth Factors. 2004;22:79-88 pubmed
    ..In particular, recent studies of an HNF4alpha-deficient mouse model demonstrate an essential role for this nuclear receptor in regulating several liver-..
  8. Adamson A, Suchankova G, Rufo C, Nakamura M, Teran Garcia M, Clarke S, et al. Hepatocyte nuclear factor-4alpha contributes to carbohydrate-induced transcriptional activation of hepatic fatty acid synthase. Biochem J. 2006;399:285-95 pubmed
    ..The findings support the broader view that HNF-4alpha is an integral component of the hepatic nutrient sensing system that co-ordinates transcriptional responses to transitions between nutritional states. ..
  9. Naiki T, Nagaki M, Shidoji Y, Kojima H, Imose M, Kato T, et al. Analysis of gene expression profile induced by hepatocyte nuclear factor 4alpha in hepatoma cells using an oligonucleotide microarray. J Biol Chem. 2002;277:14011-9 pubmed
    ..This cDNA microarray analysis showed that HNF-4alpha is one of the central liver metabolism regulators. ..
  10. Roth U, Jungermann K, Kietzmann T. Activation of glucokinase gene expression by hepatic nuclear factor 4alpha in primary hepatocytes. Biochem J. 2002;365:223-8 pubmed
    ..Venous pO2 enhanced HNF-4 levels and HNF-4 binding to the GK-HNF-4 element. Thus, HNF-4alpha could play the role of a regulator for zonated GK expression. ..
  11. Furihata T, Hosokawa M, Masuda M, Satoh T, Chiba K. Hepatocyte nuclear factor-4alpha plays pivotal roles in the regulation of mouse carboxylesterase 2 gene transcription in mouse liver. Arch Biochem Biophys. 2006;447:107-17 pubmed
    ..These findings show that HNF-4alpha plays an important role in the regulation of mCES2 gene transcription. ..
  12. Wang P, Cong M, Liu T, Xu H, Wang L, Sun G, et al. Inhibitory effects of HNF4? on migration/maltransformation of hepatic progenitors: HNF4?-overexpressing hepatic progenitors for liver repopulation. Stem Cell Res Ther. 2017;8:183 pubmed publisher
    ..The effects of HNF4? on rat hepatic progenitors (i.e. hepatic oval cells) were analyzed by HNF4? overexpression and HNF4? shRNA...
  13. Dhe Paganon S, Duda K, Iwamoto M, Chi Y, Shoelson S. Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand. J Biol Chem. 2002;277:37973-6 pubmed
    b>HNF4 alpha is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic beta cells...
  14. Petrescu A, Payne H, Boedecker A, Chao H, Hertz R, Bar Tana J, et al. Physical and functional interaction of Acyl-CoA-binding protein with hepatocyte nuclear factor-4 alpha. J Biol Chem. 2003;278:51813-24 pubmed
    ..In summary, ACBP physically interacted with HNF-4 alpha in vitro and in intact cells, although ACBP expression level directly correlated with HNF-4 alpha-mediated transactivation in individual cells. ..
  15. Laz E, Holloway M, Chen C, Waxman D. Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. Endocrinology. 2007;148:3327-37 pubmed
    ..namely, signal transducer and activator of transcription 5b (STAT5b) and hepatocyte nuclear factor 4alpha (HNF4alpha), with sex-specific expression being substantially reduced or lost in mice deficient in either nuclear factor...
  16. Huang J, Levitsky L, Rhoads D. Novel P2 promoter-derived HNF4alpha isoforms with different N-terminus generated by alternate exon insertion. Exp Cell Res. 2009;315:1200-11 pubmed
    Hepatocyte nuclear factor 4alpha (HNF4alpha) is a critical transcription factor for pancreas and liver development and functions in islet beta cells to maintain glucose homeostasis...
  17. Gao Z, Leng S, Lu F, Xie M, Xu L, Wang K. Effect of berberine on expression of hepatocyte nuclear factor-4alpha in rats with fructose-induced insulin resistance. J Huazhong Univ Sci Technolog Med Sci. 2008;28:261-5 pubmed publisher
    ..It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4alpha in liver. ..
  18. Ang S, Wierda A, Wong D, Stevens K, Cascio S, Rossant J, et al. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993;119:1301-15 pubmed
    ..HFH-E5.1 is highly similar in structure and expression profile to the Drosophila HFH gene FD4, suggesting that HFH family members have different, evolutionarily conserved roles in development. ..
  19. Wang B, Cai S, Gao C, Sladek F, Ponder K. Lipopolysaccharide results in a marked decrease in hepatocyte nuclear factor 4 alpha in rat liver. Hepatology. 2001;34:979-89 pubmed
    ..response, results in a marked decrease in the major isoforms of the transcription factor, hepatocyte nuclear factor 4 alpha (HNF-4 alpha), in livers of rats...
  20. Sandovici I, Smith N, Nitert M, Ackers Johnson M, Uribe Lewis S, Ito Y, et al. Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci U S A. 2011;108:5449-54 pubmed publisher
    ..Here, we show that the transcription factor Hnf4a, which has been implicated in the etiology of type 2 diabetes (T2D), is epigenetically regulated by maternal diet ..
  21. Zhang T, Bai Y, Wang D, Jia H, Yuan Z, Wang W. Spatiotemporal pattern analysis of transcription factor 4 in the developing anorectum of the rat embryo with anorectal malformations. Int J Colorectal Dis. 2009;24:1039-47 pubmed publisher
    ..These data implied that the downregulation of Tcf4 at the time of cloacal separation into rectum and urethra might be related to the development of ARM. ..
  22. Nedumaran B, Hong S, Xie Y, Kim Y, Seo W, Lee M, et al. DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression. J Biol Chem. 2009;284:27511-23 pubmed publisher
    ..b>HNF4alpha (hepatocyte nuclear factor 4alpha) is a liver-enriched transcription factor that controls the expression of a ..
  23. Grasfeder L, Gaillard S, Hammes S, Ilkayeva O, Newgard C, Hochberg R, et al. Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha. Mol Endocrinol. 2009;23:1171-82 pubmed publisher
    ..These data suggest that DHEA could be playing a role as an intracellular signaling molecule involved in modulating hepatic activity in response to fasting conditions. ..
  24. Kimata T, Nagaki M, Tsukada Y, Ogiso T, Moriwaki H. Hepatocyte nuclear factor-4alpha and -1 small interfering RNA inhibits hepatocyte differentiation induced by extracellular matrix. Hepatol Res. 2006;35:3-9 pubmed
  25. Pare J, Malenfant D, Courtemanche C, Jacob Wagner M, Roy S, Allard D, et al. The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem. 2004;279:21206-16 pubmed
    ..The FTF-lacZ mouse establishes a central role for FTF in developmental, nutritive, and metabolic functions from early embryogenesis through adulthood. ..
  26. Massillon D, Arinze I, Xu C, Bone F. Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha. J Biol Chem. 2003;278:40694-701 pubmed
  27. Masuda N, Yasumo H, Furusawa T, Tsukamoto T, Sadano H, Osumi T. Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors. Gene. 1998;221:225-33 pubmed
    ..NRBF-1 has a significant homology to the yeast protein MRF1, a putative transcription factor regulating the expression of mitochondrial respiratory proteins. NRBF-1 might be another type of nuclear receptor co-operator. ..
  28. Wang Z, Burke P. Hepatocyte nuclear factor-4? interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression. FEBS J. 2010;277:4066-75 pubmed publisher
    ..These findings provide new insights into the mechanism of the negative transcriptional regulation of the transthyretin gene after injury caused by a decrease in the binding of HNFs and a modulation in their coordinated interactions. ..
  29. Menjivar M, Granados Silvestre M, Montufar Robles I, Herrera M, Tusie Luna M, Canizales Quinteros S, et al. High frequency of T130I mutation of HNF4A gene in Mexican patients with early-onset type 2 diabetes. Clin Genet. 2008;73:185-7 pubmed
  30. Wisely G, Miller A, Davis R, Thornquest A, Johnson R, Spitzer T, et al. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure. 2002;10:1225-34 pubmed
    ..GC/MS and NMR analysis of chloroform/methanol extracts from purified HNF4alpha and HNF4gamma LBDs identified mixtures of saturated and cis-monounsaturated C14-18 fatty acids...
  31. Flanagan S, Kapoor R, Mali G, Cody D, Murphy N, Schwahn B, et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol. 2010;162:987-92 pubmed publisher
    The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY)...
  32. Ning B, Ding J, Yin C, Zhong W, Wu K, Zeng X, et al. Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma. Cancer Res. 2010;70:7640-51 pubmed publisher
    Hepatocyte nuclear factor 4? (HNF4?) is a transcription factor that plays a key role in hepatocyte differentiation and the maintenance of hepatic function, but its role in hepatocarcinogenesis has yet to be examined...
  33. Petrescu A, Hertz R, Bar Tana J, Schroeder F, Kier A. Ligand specificity and conformational dependence of the hepatic nuclear factor-4alpha (HNF-4alpha ). J Biol Chem. 2002;277:23988-99 pubmed
    ..In summary, these data demonstrate for the first time high affinity binding to HNF-4alpha of fatty and xenobiotic acyl-CoAs in the physiological range, resulting in significantly altered HNF-4alpha conformation. ..
  34. Pooya S, Blaise S, Moreno Garcia M, Giudicelli J, Alberto J, Guéant Rodriguez R, et al. Methyl donor deficiency impairs fatty acid oxidation through PGC-1? hypomethylation and decreased ER-?, ERR-?, and HNF-4? in the rat liver. J Hepatol. 2012;57:344-51 pubmed publisher
    ..This link between methyl donor deficiency and epigenomic deregulations of energy metabolism opens new insights into the pathogenesis of fatty liver disease, in particular, in relation to the fetal programming hypothesis. ..
  35. Louet J, Hayhurst G, Gonzalez F, Girard J, Decaux J. The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). J Biol Chem. 2002;277:37991-8000 pubmed
    ..that the coactivator PGC-1 is involved in the regulation of this gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB)...
  36. Yamasaki H, Sada A, Iwata T, Niwa T, Tomizawa M, Xanthopoulos K, et al. Suppression of C/EBPalpha expression in periportal hepatoblasts may stimulate biliary cell differentiation through increased Hnf6 and Hnf1b expression. Development. 2006;133:4233-43 pubmed
    ..Wild-type hepatoblasts constructed mature hepatic tissue accompanied by biliary cell differentiation. These results also demonstrate that the suppression of C/EBPalpha expression may stimulate biliary cell differentiation. ..
  37. Naiki T, Nagaki M, Asano T, Kimata T, Moriwaki H. Adenovirus-mediated hepatocyte nuclear factor-4alpha overexpression maintains liver phenotype in cultured rat hepatocytes. Biochem Biophys Res Commun. 2005;335:496-500 pubmed
  38. Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez F, Talianidis I. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006;20:2293-305 pubmed
    ..The results illustrate the remarkable flexibility of a self-sustaining transcription factor network, built up by complex dominant and redundant regulatory motifs in developing hepatocytes. ..
  39. Dietrich C, Martin I, Porn A, Voigt S, Gartung C, Trautwein C, et al. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha. Am J Physiol Gastrointest Liver Physiol. 2007;293:G585-90 pubmed
    ..adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway...
  40. Hertz R, Kalderon B, Byk T, Berman I, Za tara G, Mayer R, et al. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}. J Biol Chem. 2005;280:24451-61 pubmed
    ..The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors. ..
  41. Park E, Lee C, Lee E, Kim J, Cova A, Lee S, et al. HNF4? contributes to glucose formation in aged rat hepatocytes. Exp Gerontol. 2013;48:1518-25 pubmed publisher
    ..Furthermore, the hepatocyte nuclear factor ? (HNF4?) protein, but not the HNF4? mRNA level, increased in parallel with the PEPCK mRNA expression under hypoxic ..
  42. Einstein F, Thompson R, Bhagat T, Fazzari M, Verma A, Barzilai N, et al. Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS ONE. 2010;5:e8887 pubmed publisher
    ..loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other ..
  43. Chen W, Manova K, Weinstein D, Duncan S, Plump A, Prezioso V, et al. Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev. 1994;8:2466-77 pubmed
    ..Development of embryonic structures is severely impaired. These results demonstrate that the expression of HNF-4 in the visceral endoderm is essential for embryonic ectoderm survival and normal gastrulation. ..
  44. Mar Heyming R, Miyazaki M, Weissglas Volkov D, Kolaitis N, Sadaat N, Plaisier C, et al. Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2008;28:1193-9 pubmed publisher
    ..21 to 20q13.32 (z = 1.7, P = 0.04), containing the hepatocyte nuclear factor 4, alpha (HNF4alpha) gene...
  45. Sirard C, de la Pompa J, Elia A, Itie A, Mirtsos C, Cheung A, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev. 1998;12:107-19 pubmed
    ..Rescued embryos show severe anterior truncations, indicating a second important role for Smad4 in anterior patterning during embryogenesis. ..
  46. López Soldado I, Avella M, Botham K. Suppression of VLDL secretion by cultured hepatocytes incubated with chylomicron remnants enriched in n-3 polyunsaturated fatty acids is regulated by hepatic nuclear factor-4alpha. Biochim Biophys Acta. 2009;1791:1181-9 pubmed publisher
    ..These findings suggest that the direct suppression of VLDL secretion by dietary n-3 PUFA delivered to the liver in CMR is mediated via decreased expression of HNF-4alpha. ..
  47. Viollet B, Kahn A, Raymondjean M. Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4. Mol Cell Biol. 1997;17:4208-19 pubmed
    Hepatocyte nuclear factor 4 (HNF4), a liver-enriched transcription factor of the nuclear receptor superfamily, is critical for development and liver-specific gene expression...
  48. Torres Padilla M, Weiss M. Effects of interactions of hepatocyte nuclear factor 4alpha isoforms with coactivators and corepressors are promoter-specific. FEBS Lett. 2003;539:19-23 pubmed
    The gene encoding hepatocyte nuclear factor 4alpha (HNF4alpha) possesses two alternative promoters responsible for developmental and tissue-specific expression of HNF4alpha1 and HNF4alpha7...
  49. Grigo K, Wirsing A, Lucas B, Klein Hitpass L, Ryffel G. HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells. Biol Chem. 2008;389:179-87 pubmed publisher
    ..The cell-specific transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha) is down-regulated in RCC and we have shown that HNF4 alpha inhibits cell proliferation ..
  50. Xu Z, Tavares Sanchez O, Li Q, Fernando J, Rodriguez C, Studer E, et al. Activation of bile acid biosynthesis by the p38 mitogen-activated protein kinase (MAPK): hepatocyte nuclear factor-4alpha phosphorylation by the p38 MAPK is required for cholesterol 7alpha-hydroxylase expression. J Biol Chem. 2007;282:24607-14 pubmed
    ..These studies show a functional link between the p38 signaling pathway, HNF-4alpha, and bile acid synthesis. ..
  51. Adachi S, Jigami T, Yasui T, Nakano T, Ohwada S, Omori Y, et al. Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling. Cancer Res. 2004;64:8496-501 pubmed
    ..These results suggest that B9L plays an important role in tumorigenesis induced by aberrant activation of Wnt signaling. ..
  52. Chiba H, Sakai N, Murata M, Osanai M, Ninomiya T, Kojima T, et al. The nuclear receptor hepatocyte nuclear factor 4alpha acts as a morphogen to induce the formation of microvilli. J Cell Biol. 2006;175:971-80 pubmed
    ..we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), triggers microvillus morphogenesis...
  53. Sadagurski M, Yakar S, Weingarten G, Holzenberger M, Rhodes C, Breitkreutz D, et al. Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation. Mol Cell Biol. 2006;26:2675-87 pubmed
    ..In conclusion, these results reveal that IGF-1R plays an inhibitory role in the regulation of skin development and differentiation. ..