간X수용체α
Liver X receptor alpha
간 X수용체 알파(LXR-alpha)는 NR1H3 유전자(핵수용체 서브패밀리 1, 그룹 H, [5][6]멤버 3)에 의해 인간에서 암호화되는 핵수용체 단백질이다.
표현
miRNA hsa-miR-613은 LXRα 3µ-untranslated 영역 내의 특정 miRNA 응답 요소(613MRE)를 통해 내인성 LXRα를 목표로 하여 인간의 LXRα 유전자를 자동 조절한다.LXRα는 miRNA has-miR-613을 [7]상향 조절하는 SREBP1c의 유도를 통해 자체 억제를 조절한다.
기능.
간 X 수용체인 LXRα(이 단백질)와 LXRβ는 핵 수용체 슈퍼패밀리의 하위 패밀리를 형성하며 대식세포 기능의 핵심 조절제로서 지질 항상성과 염증에 관여하는 전사 프로그램을 제어한다.또한, 그것들은 디오디나아제를 [8]통한 갑상선 호르몬의 국소 활성화에 중요한 역할을 합니다.유도성 LXRα는 간, 부신, 장, 지방 조직, 대식세포, 폐 및 신장에서 높게 발현되는 반면, LXRβ는 어디서나 발현된다.리간드 활성화 LXR은 레티노이드 X 수용체(RXR)와 결합하는 헤테로디머를 형성하고 LXR 반응 [9][10]요소를 포함하는 표적 유전자의 발현을 조절한다.건선 병변 내에서 LXR-알파 발현/기능을 복원하면 건선에서 무증상 피부로 [11]전환하는 데 도움이 될 수 있습니다.
상호 작용
간 X 수용체 알파는 EDF1[12] 및 소형 헤테로디머 [13]파트너와 상호작용하는 것으로 나타났다.LXRα는 전사인자 SREBP-1c를 활성화하여 지방 [14]형성을 일으킨다.
다발성 경화증과의 연관성
2016년 연구에 따르면 두 가족 중 70%가 NR1H3에 [15]돌연변이가 있었다.그러나 13배 더 큰 표본 크기를 사용한 국제 다발성 경화증 유전학 컨소시엄의 분석에서는 문제의 돌연변이가 있다는 증거를 찾을 수 없었다(p).Arg415Gln)은 다발성 경화증과 관련되며 이러한 발견을 [16]반박한다.
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG000025434 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG00000002108 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Miyata KS, McCaw SE, Patel HV, Rachubinski RA, Capone JP (Apr 1996). "The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling". The Journal of Biological Chemistry. 271 (16): 9189–92. doi:10.1074/jbc.271.16.9189. PMID 8621574.
- ^ Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ (May 1995). "LXR, a nuclear receptor that defines a distinct retinoid response pathway". Genes & Development. 9 (9): 1033–45. doi:10.1101/gad.9.9.1033. PMID 7744246.
- ^ http://mend.endojournals.org/content/25/4/584.abstract[데드링크]
- ^ Christoffolete MA, Doleschall M, Egri P, Liposits Z, Zavacki AM, Bianco AC, Gereben B (2010). "Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway". The Journal of Endocrinology. 205 (2): 179–86. doi:10.1677/JOE-09-0448. PMC 3133926. PMID 20176747.
- ^ Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B, Gustafsson JA, Grooten J, Huygen K (Jun 2009). "Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice". The Journal of Clinical Investigation. 119 (6): 1626–37. doi:10.1172/JCI35288. PMC 2689129. PMID 19436111.
- ^ "Entrez Gene: nuclear receptor subfamily 1".
- ^ Gupta DS, Kaul D, Kanwar AJ, Parsad D (Jan 2010). "Psoriasis: crucial role of LXR-alpha RNomics". Genes and Immunity. 11 (1): 37–44. doi:10.1038/gene.2009.63. PMID 19798078.
- ^ Brendel C, Gelman L, Auwerx J (Jun 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology. 16 (6): 1367–77. doi:10.1210/mend.16.6.0843. PMID 12040021.
- ^ Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (Sep 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
- ^ Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, Unger RH (2010). "Leptin therapy in insulin-deficient type I diabetes". Proceedings of the National Academy of Sciences of the United States of America. 107 (11): 4813–9. doi:10.1073/pnas.0909422107. PMC 2841945. PMID 20194735.
- ^ Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, Yee IM, de Lemos M, Greenwood T, Lee JD, Wright G, Ross CJ, Zhang S, Song W, Vilariño-Güell C (2016). "Nuclear Receptor NR1H3 in Familial Multiple Sclerosis". Neuron. 90 (5): 948–54. doi:10.1016/j.neuron.2016.04.039. PMC 5092154. PMID 27253448.
- ^ Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, et al. (International Multiple Sclerosis Genetics Consortium) (October 2016). "NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk". Neuron. 92 (2): 333–335. doi:10.1016/j.neuron.2016.09.052. PMC 5641967. PMID 27764667.
추가 정보
- Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM (Feb 1997). "Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway". The Journal of Biological Chemistry. 272 (6): 3137–40. doi:10.1074/jbc.272.6.3137. PMID 9013544.
- Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H (Aug 1997). "Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients". Diabetes. 46 (8): 1319–27. doi:10.2337/diabetes.46.8.1319. PMID 9231657.
- Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ (May 1998). "Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha". Cell. 93 (5): 693–704. doi:10.1016/S0092-8674(00)81432-4. PMID 9630215. S2CID 5856580.
- Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone JP (Nov 1998). "Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha". Molecular and Cellular Endocrinology. 146 (1–2): 69–76. doi:10.1016/S0303-7207(98)00196-8. PMID 10022764. S2CID 53253694.
- Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P (Oct 2000). "Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha". Proceedings of the National Academy of Sciences of the United States of America. 97 (22): 12097–102. Bibcode:2000PNAS...9712097V. doi:10.1073/pnas.200367697. PMC 17300. PMID 11035776.
- Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B (Jan 2001). "PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway". Nature Medicine. 7 (1): 53–8. doi:10.1038/83348. PMID 11135616. S2CID 20558311.
- Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P (Jan 2001). "LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes". Proceedings of the National Academy of Sciences of the United States of America. 98 (2): 507–12. doi:10.1073/pnas.021488798. PMC 14617. PMID 11149950.
- Li Y, Bolten C, Bhat BG, Woodring-Dietz J, Li S, Prayaga SK, Xia C, Lala DS (Mar 2002). "Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism". Molecular Endocrinology. 16 (3): 506–14. doi:10.1210/mend.16.3.0789. PMID 11875109.
- Mak PA, Laffitte BA, Desrumaux C, Joseph SB, Curtiss LK, Mangelsdorf DJ, Tontonoz P, Edwards PA (Aug 2002). "Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta". The Journal of Biological Chemistry. 277 (35): 31900–8. doi:10.1074/jbc.M202993200. PMID 12032151.
- Brendel C, Gelman L, Auwerx J (Jun 2002). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism". Molecular Endocrinology. 16 (6): 1367–77. doi:10.1210/mend.16.6.0843. PMID 12040021.
- Steffensen KR, Schuster GU, Parini P, Holter E, Sadek CM, Cassel T, Eskild W, Gustafsson JA (May 2002). "Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins". Biochemical and Biophysical Research Communications. 293 (5): 1333–40. doi:10.1016/S0006-291X(02)00390-X. PMID 12054659.
- Gbaguidi GF, Agellon LB (Jul 2002). "The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1583 (2): 229–36. doi:10.1016/s1388-1981(02)00217-2. PMID 12117567.
- Pawar A, Xu J, Jerks E, Mangelsdorf DJ, Jump DB (Oct 2002). "Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells". The Journal of Biological Chemistry. 277 (42): 39243–50. doi:10.1074/jbc.M206170200. PMID 12161442.
- Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (Sep 2002). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Molecular Endocrinology. 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
- Oberkofler H, Schraml E, Krempler F, Patsch W (Apr 2003). "Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha". The Biochemical Journal. 371 (Pt 1): 89–96. doi:10.1042/BJ20021665. PMC 1223253. PMID 12470296.
- Wang M, Thomas J, Burris TP, Schkeryantz J, Michael LF (Nov 2003). "Molecular determinants of LXRalpha agonism". Journal of Molecular Graphics & Modelling. 22 (2): 173–81. doi:10.1016/S1093-3263(03)00159-1. PMID 12932788.
- Fukuchi J, Song C, Ko AL, Liao S (Sep 2003). "Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors". Steroids. 68 (7–8): 685–91. doi:10.1016/S0039-128X(03)00100-4. PMID 12957674. S2CID 6023862.
외부 링크
- UCSC Genome Browser의 NR1H3 인간 유전자 위치.
- UCSC Genome Browser의 NR1H3 인간 유전자 상세.
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