WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
of or relating to or constituting the nucleus of an atom; "nuclear physics"; "nuclear fission"; "nuclear forces"
(weapons) deriving destructive energy from the release of atomic energy; "nuclear war"; "nuclear weapons"; "atomic bombs" (同)atomic
constituting or like a nucleus; "annexation of the suburban fringe by the nuclear metropolis"; "the nuclear core of the congregation"
of or relating to or constituting the nucleus of a cell; "nuclear membrane"; "nuclear division"

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
『核の』,細胞核の / [『原子』]『核の』

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/28 19:13:12」(JST)

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[Wiki en表示]

HNF4 (Hepatocyte Nuclear Factor 4) is a nuclear receptor protein mostly expressed in the liver, gut, kidney, and pancreatic beta cells that is critical for liver development. In humans, there are two isoforms of HNF4, HNF4α and HNF4γ, encoded by two separate genes HNF4A and HNF4G respectively.^[1]

Ligands

HNF4 was originally classified as an orphan receptor that exhibits constitutive transactivation activity apparently by being continuously bound to a variety of fatty acids.^[2]^[3] The existence of a ligand for HNF4 has been somewhat controversial, but linoleic acid (LA) has been identified as the endogenous ligand of native HNF4 expressed in mouse liver; the binding of LA to HNF4 is reversible.^[4]

The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich fold^[5]^[6] and interacts with co-activator proteins.^[7]

HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription.

Pathology

Mutations in the HNF4A gene have been linked to maturity onset diabetes of the young 1 (MODY1).^[8]

This seems to be caused by HNF4-a's [1] role in the synthesis of SHBG, which is known to be severely diminished in patients with insulin-resistance.

References

^ Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (1994). "Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver". Gene 147 (2): 269–72. doi:10.1016/0378-1119(94)90079-5. PMID 7926813.
^ Sladek F (August 2002). "Desperately seeking...something". Mol. Cell 10 (2): 219–21. doi:10.1016/S1097-2765(02)00605-6. PMID 12191466.
^ Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O (November 2005). "Fatty acid regulation of hepatic gene transcription". J. Nutr. 135 (11): 2503–6. PMID 16251601.
^ Yuan X, Ta TC, Lin M, Evans JR, Dong Y, Bolotin E, Sherman MA, Forman BM, Sladek FM (2009). "Identification of an endogenous ligand bound to a native orphan nuclear receptor". In Laudet, Vincent. PLoS ONE 4 (5): e5609. doi:10.1371/journal.pone.0005609. PMC 2680617. PMID 19440305.
^ Wisely GB, Miller AB, Davis RG, Thornquest AD, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, Willson TM, Williams SP (September 2002). "Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids". Structure 10 (9): 1225–34. doi:10.1016/S0969-2126(02)00829-8. PMID 12220494.
^ Dhe-Paganon S, Duda K, Iwamoto M, Chi YI, Shoelson SE (October 2002). "Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand". J. Biol. Chem. 277 (41): 37973–6. doi:10.1074/jbc.C200420200. PMID 12193589.
^ Duda K, Chi YI, Shoelson SE (May 2004). "Structural basis for HNF-4alpha activation by ligand and coactivator binding". J. Biol. Chem. 279 (22): 23311–6. doi:10.1074/jbc.M400864200. PMID 14982928.
^ Fajans SS, Bell GI, Polonsky KS (2001). "Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young". N Engl J Med 345 (13): 971–80. doi:10.1056/NEJMra002168. PMID 11575290.

External links

Hepatocyte Nuclear Factor 4 at the US National Library of Medicine Medical Subject Headings (MeSH)

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UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 糖尿病および遺伝的糖尿病症候群の分類 classification of diabetes mellitus and genetic diabetic syndromes
2. 赤血球産生調節 regulation of erythropoiesis
3. 血友病の遺伝学 genetics of the hemophilias
4. 幼児の持続性高インスリン血症性低血糖症の病因、臨床的特徴、および診断 pathogenesis clinical features and diagnosis of persistent hyperinsulinemic hypoglycemia of infancy

English Journal

Inhibition of hepatitis B Virus replication by hepatocyte nuclear factor 4-alpha specific short hairpin RNA.

He F, Chen EQ, Liu L, Zhou TY, Liu C, Cheng X, Liu FJ, Tang H.SourceCenter of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
Liver international : official journal of the International Association for the Study of the Liver.Liver Int.2012 Feb 18. doi: 10.1111/j.1478-3231.2011.02748.x. [Epub ahead of print]
BACKGROUND: Previous studies showed that hepatocyte nuclear factor 4α (HNF4α) may play a critical role in hepatitis B virus (HBV) replication.AIMS: This study aimed to investigate the effect of knocking down of HNF4α with RNA interference technique on HBV replication in a HBV replication mouse mo
PMID 22340507

Transcriptional expression profile of cultured human embryonic stem cells in vitro and in vivo.

Keil M, Siegert A, Eckert K, Gerlach J, Haider W, Fichtner I.SourceMax-Delbrück-Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Str. 10, 13125, Berlin, Germany, m.keil@mdc-berlin.de.
In vitro cellular & developmental biology. Animal.In Vitro Cell Dev Biol Anim.2012 Feb 4. [Epub ahead of print]
The aims of this study were to analyze the spontaneous differentiation of human embryonic stem cells in vitro and in vivo and to investigate the influence of in vitro partial differentiation on in vivo teratoma formation in immunodeficient mice. Standardized methods are needed for long-term cultivat
PMID 22311374

Japanese Journal

ヒト肝細胞癌におけるHepatocyte nuclear factor 4αの発現に関する研究

戸枝路子
新潟医学会雑誌 126(3), 138-148, 2012-03
NAID 40019412603

Short-Chain Fatty Acids Increase the Level of Calbindin-D9k Messenger RNA in Caco-2 Cells

FUKUSHIMA Akiko,AIZAKI Yoshimi,SAKUMA Keiko
Journal of Nutritional Science and Vitaminology 58(4), 287-291, 2012
… To test this hypothesis, SCFAs were added to Caco-2 human intestinal epithelial cells, and changes in the levels of transcription of genes for calbindin-D9k, and transcription factors (vitamin D receptor: VDR, caudal homeobox-2: Cdx-2, hepatocyte nuclear factor 1-α: HNF1-α) were determined by quantitative reverse transcription polymerase chain reaction. …
NAID 130002103020

Interruption of Hepatocyte Growth Factor Signaling Augmented Oridonin-Induced Death in Human Non-small Cell Lung Cancer A549 Cells via c-Met-Nuclear Factor-κB-Cyclooxygenase-2 and c-Met-Bcl-2-Caspase-3 Pathways

Liu Ying,Shi Qi-Feng,Qi Min,Tashiro Shin-Ichi,Onodera Satoshi,Ikejima Takashi
Biological and Pharmaceutical Bulletin 35(7), 1150-1158, 2012
… The aim of this study was to elucidate the molecular mechanisms mediating hepatocyte growth factor (HGF)-induced protection against oridonin-induced apoptosis in A549 cells. … HGF-induced protective effect was partially attributed to the activation of nuclear factor (NF)-κB and cyclooxygenase 2 (COX-2), since the protective effect was abolished by inhibition of NF-κB or interruption of COX-2. …
NAID 130001872123

Related Pictures

★リンクテーブル★

リンク元	「HNF-4」「肝細胞核因子4」
関連記事	「nuclear」「fact」「factor」「nuclear factor」

「HNF-4」

Hepatocyte nuclear factor 4 gamma
Identifiers
Symbol	HNF4G
Entrez	3174
HUGO	5026
OMIM	605966
PDB	1LV2 (RCSB PDB PDBe PDBj)
RefSeq	NM_004133
UniProt	Q14541
Other data
Locus	Chr. 8 q21-q22

Hepatocyte nuclear factor 4 alpha
Identifiers
Symbol	HNF4A
Alt. symbols	TCF14, MODY, MODY1
Entrez	3172
HUGO	5024
OMIM	600281
PDB	1M7W (RCSB PDB PDBe PDBj)
RefSeq	NM_001030004
UniProt	P41235
Other data
Locus	Chr. 20 q12-20q13.1