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the 14th letter of the Roman alphabet (同)n

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nitrogenの化学記号
『私の』 / 《親しみをこめた呼び掛けに用いて》 / 《驚きを表して》おや,まあ
neodymiumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/21 15:58:24」(JST)

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N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.

Function

The MYCN gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA.^[1] N-Myc is highly expressed in the fetal brain and is critical for normal brain development.^[2]

The MYCN gene has an antisense RNA, N-cym or MYCNOS, transcribed from the opposite strand which can be translated to form a protein product.^[3] N-Myc and MYCNOS are co-regulated both in normal development and in tumor cells, so it is possible that the two proteins are functionally related.^[4] It has been shown that NCYM antisense RNA encodes for a protein that has originated de novo and is specific to human and chimpanzee. This NCYM protein inhibits GSK3b and thus prevents MYCN degradation. Transgenic mice that harbor human MYCN/NCYM pair often show neuroblastomas with distant metastasis, which are atypical for normal mice. Thus NCYM represents a rare example of a de novo gene that has acquired molecular function and plays a major role in oncogenesis. ^[5]

Clinical significance

Amplification and overexpression of N-Myc can lead to tumorigenesis. Excess N-Myc is associated with a variety of tumors, most notably neuroblastomas where patients with amplification of the N-Myc gene tend to have poor outcomes.^[6]^[7]^[8]

Interactions

N-Myc has been shown to interact with MAX.^[9]^[10]

N-Myc is also stabilized by aurora A which protects it from degradation.^[11] Drugs that target this interaction are under development, and are designed to change the conformation of aurora A. Conformational change in Aurora A leads to release of N-Myc, which is then degraded in a ubiquitin-dependent manner.^[12]

References

^ "Entrez Gene: MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)".
^ Knoepfler PS, Cheng PF, Eisenman RN (2002). "N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation.". Genes Dev. 16 (20): 2699–712. doi:10.1101/gad.1021202. PMID 12381668.
^ Armstrong BC, Krystal GW (1992). "Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc.". Cell Growth Differ. 3 (6): 385–90. PMID 1419902.
^ "MYCN opposite strand/antisense RNA [Homo sapiens]". Entrez Gene Database. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Suenaga Y, Islam SM, Alagu J, Kaneko Y, Kato M, Tanaka Y, Kawana H, Hossain S, Matsumoto D, Yamamoto M, Shoji W, Itami M, Shibata T, Nakamura Y, Ohira M, Haraguchi S, Takatori A, Nakagawara A (2014). "NCYM, a Cis-Antisense Gene of MYCN, Encodes a De Novo Evolved Protein That Inhibits GSK3β Resulting in the Stabilization of MYCN in Human Neuroblastomas". PLoS Genetics 10 (1): e1003996. doi:10.1371/journal.pgen.1003996. PMID 24391509.
^ Cheng JM, Hiemstra JL, Schneider SS, Naumova A, Cheung NK, Cohn SL, Diller L, Sapienza C, Brodeur GM (June 1993). "Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas". Nat. Genet. 4 (2): 191–4. doi:10.1038/ng0693-191. PMID 8102299.
^ Emanuel BS, Balaban G, Boyd JP, Grossman A, Negishi M, Parmiter A, Glick MC (1985). "N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas.". Proc. Natl. Acad. Sci. U.S.A. 82 (11): 3736–40. doi:10.1073/pnas.82.11.3736. PMC 397862. PMID 2582423.
^ Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984). "Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.". Science 224 (4653): 1121–4. doi:10.1126/science.6719137. PMID 6719137.
^ Blackwood EM, Eisenman RN (March 1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science 251 (4998): 1211–7. doi:10.1126/science.2006410. PMID 2006410.
^ FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (April 1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc". Oncogene 18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID 10229200.
^ Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, Berwanger B, Eilers M (January 2009). "Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma". Cancer Cell 15 (1): 67–78. doi:10.1016/j.ccr.2008.12.005. PMID 19111882.
^ Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, Eilers M, Shokat KM, Weiss WA (Aug 27, 2014). "Drugging MYCN through an Allosteric Transition in Aurora Kinase A.". Cancer Cell 26: 414–27. doi:10.1016/j.ccr.2014.07.015. PMID 25175806.

External links

MYCN protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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1. バーキットリンパ腫の病理学 pathobiology of burkitt lymphoma
2. びまん性大細胞型B細胞性リンパ腫の予後 prognosis of diffuse large b cell lymphoma
3. びまん性大細胞型B細胞性リンパ腫および原発性縦隔大細胞型B細胞リンパ腫の病理学 pathobiology of diffuse large b cell lymphoma and primary mediastinal large b cell lymphoma
4. 髄芽腫の治療および予後 treatment and prognosis of medulloblastoma
5. 進行期びまん性大細胞型B細胞性リンパ腫の初期治療 initial treatment of advanced stage diffuse large b cell lymphoma

English Journal

NDRG1 overexpressing gliomas are characterized by reduced tumor vascularization and resistance to antiangiogenic treatment.

Broggini T1, Wüstner M1, Harms C2, Stange L1, Blaes J3, Thomé C3, Harms U4, Mueller S4, Weiler M3, Wick W3, Vajkoczy P1, Czabanka M5.
Cancer letters.Cancer Lett.2016 Oct 1;380(2):568-76. doi: 10.1016/j.canlet.2015.06.026. Epub 2015 Aug 20.
Hypoxia-regulated molecules play an important role in vascular resistance to antiangiogenic treatment. N-myc downstream-regulated-gene 1 (NDRG1) is significantly upregulated during hypoxia in glioma. It was the aim of the present study to analyze the role of NDRG1 on glioma angiogenesis and on antia
PMID 26297987

The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.

King B1,2,3, Boccalatte F1,2, Moran-Crusio K1,2,4, Wolf E5, Wang J1,2, Kayembe C1,2, Lazaris C1,2,6, Yu X1,2, Aranda-Orgilles B1,2, Lasorella A7, Aifantis I1,2.
Nature immunology.Nat Immunol.2016 Sep 26. doi: 10.1038/ni.3559. [Epub ahead of print]
Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. We identified the ubiquitin ligase Huwe1 as a crucial regulator of HSC function via its post-translational control of the oncoprotein N-myc (encoded
PMID 27668798

Field Cancerization in Sporadic Colon Cancer.

Park SK1,2, Song CS1,2, Yang HJ1,2, Jung YS1,2, Choi KY1,2, Koo DH1,2, Kim KE2,3, Jeong KU2,4, Kim HO2,4, Kim H2,4, Chun HK2,4, Park DI1,2.
Gut and liver.Gut Liver.2016 Sep 15;10(5):773-80. doi: 10.5009/gnl15334.
BACKGROUND/AIMS: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have pr
PMID 27114416

Japanese Journal

Unexpected Intraparenchymal Hematoma Caused by Brain Metastasis in a Patient With Neuroblastoma : Case Report

OKURA Hidehiro,YATOMI Kenji,SAITO Youhei,KASUGA Chinatsu,ISHII Hisato,KARAGIOZOV Kostadin,MIYAJIMA Masakazu,ARAI Hajime
Neurologia medico-chirurgica = 神経外科 51(11), 784-788, 2011-11-15
… The related factors in this patient with abdominal neuroblastoma included elevated serum lactate dehydrogenase, N-myc gene amplification, and coexisting orbital metastasis, which all occurred within 22 months from initial diagnosis. …
NAID 10030030426

The effect of Ndrg2 expression on astroglial activation

Takeichi Toshiaki,Takarada-Iemata Mika,Hashida Koji,Sudo Hirofumi,Okuda Tomohiko,Kokame Koichi,Hatano Taku,Takanashi Masashi,Funabe Sayaka,Hattori Nobutaka,Kitamura Osamu,Kitao Yasuko,Hori Osamu
Neurochemistry International 59(1), 21-27, 2011-08-00
… N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the central nervous system (CNS). …
NAID 120003221535

Suppression of N-Myc Downstream-Regulated Gene 2 Is Associated with Induction of Myc in Colorectal Cancer and Correlates Closely with Differentiation

Shi Hai,Jin Haifeng,Chu Dake [他],Wang Weizhong,Zhang Jian,Chen Changsheng,Xu Chunsheng,Fan Daiming,Yao Libo
Biological and Pharmaceutical Bulletin 32(6), 968-975, 2009
… NDRG2, a new member of the N-Myc downstream-regulated gene (NDRG) family, is a focus for study at present. … In this study, using a colorectal cancer tissue array and a series of 213 colorectal cancer samples, the relationship between Ndrg2 and c-MYC expression and tumor differentiation level was investigated. … Immunohistochemistry showed that Ndrg2 expression was reduced and that c-Myc was increased in colorectal carcinomas. …
NAID 130000117172

Related Pictures

Figure 6. Figure 1. Vector for expressing an N-terminally Myc The normal n-myc locus on 2p24, and MYC in mammalian epidermis: how can an myc myc_Neurolastoma

★リンクテーブル★

リンク元	「神経芽細胞腫」「癌遺伝子」
拡張検索	「N-myc gene」「N-myc遺伝子」
関連記事	「n」「my」「N」「Nd」

「神経芽細胞腫」

V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog
Identifiers
Symbols	MYCN ; MODED; N-myc; NMYC; ODED; bHLHe37
External IDs	OMIM: 164840 MGI: 97357 HomoloGene: 3922 GeneCards: MYCN Gene
Gene ontology
Molecular function	• DNA binding; • sequence-specific DNA binding transcription factor activity; • protein binding; • protein dimerization activity;
Cellular component	• chromatin; • nucleus;
Biological process	• cartilage condensation; • positive regulation of mesenchymal cell proliferation; • regulation of transcription from RNA polymerase II promoter; • positive regulation of cell death; • lung development; • embryonic digit morphogenesis; • positive regulation of transcription, DNA-templated; • positive regulation of transcription from RNA polymerase II promoter; • embryonic skeletal system morphogenesis; • negative regulation of astrocyte differentiation; • branching morphogenesis of an epithelial tube; • negative regulation of reactive oxygen species metabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: neuroblastoma NB
同: 神経芽腫、交感神経芽細胞腫 sympathoblastoma

[show details]

神経芽細胞腫 : 約 103,000 件
神経芽腫 : 約 68,600 件

概念

病因

神経堤細胞から派生した交感神経原細胞に由来
脊柱傍部の交感神経節や副腎髄質(大多数(約65%))から発生。

頚部、後縦隔、後腹膜など

疫学

小児期の悪性腫瘍の10-15%を占める
小児固形腫瘍の中で最も頻度が高い (次に多いのがWilms腫瘍)
5歳以下で発症

進展形式

神経芽細胞は早期に骨髄浸潤をきたしやすい。

病態

全身に進展しうる。
骨髄に進展すれば、造血能の低下から貧血をきたす。
眼窩周囲に進展してすることにより眼症状を呈する。

症状

非特異的で、腫瘍が進展してから発見されることが多い

腹部・頚部：硬い腫瘤を触れる
全身症状：顔色不良、貧血、食欲不振
眼症状：眼球突出、眼瞼周囲の皮下出血

検査

血液検査

NSE：陽性
LDH：高値

腫瘍マーカーの尿・血液からの検出。症例の70-80%に尿中のHVA, VMAの出現を見る

尿中ホモバリニン酸(HVA)、尿中バニリルマンデル酸(VMA)、血中神経特異性エノラーゼ(NSE)

画像検査：CT, MRI, 超音波検査で原発巣と転移を判断。

単純X線検査：石灰化像を認めることがある。

骨髄穿刺

骨髄浸潤を判定するために必須。

診断

白血病との鑑別が必要。

治療

限局例：手術
進行例：全身化学療法、造血細胞移植＋超大量化学療法

予後

進行例ではきわめて予後不良。
1歳未満発症でかつN-myc遺伝子増幅がなければ予後良好
1歳以上の患児における5年無病生存率：病期III 70%。病期IV 30%

予後良好因子と予後不良因子

予後良好因子・・・1歳未満(病期I、II、III、IVs)

予後不良因子・・・1歳以上の病期III、IV。二倍体。trk遺伝子未発現。染色体1p欠失。N-myc遺伝子の増殖。

予防

新生児スクリーニングとしては実施されていない
乳児期(6ヶ月)にスクリーニングが行われる？(小児科学第2版p.263)

「癌遺伝子」

　　[★]

英: oncogene
同: オンコジーン、腫瘍遺伝子、発癌遺伝子、がん遺伝子、発がん遺伝子
関: 癌抑制遺伝子

原癌遺伝子に変異が導入されて原癌遺伝子の働きが異常になった場合、この状態の遺伝子を癌遺伝子という。
K-ras、c-erbB2、N-myc、c-myc、c-abl/bcr、Bcl-2

「N-myc gene」

　　[★]

N-myc遺伝子

関: c-myc gene、c-myc proto-oncogene、myc gene、myc oncogene

「N-myc遺伝子」

　　[★]

英: N-myc gene
関: c-myc遺伝子、myc遺伝子、c-myc癌原遺伝子

「n」

　　[★]

n.

例数

関: number of experiment、sample size

pの前の[n]はmと記載する。synptom→symptom

「my」

　　[★]

comb form.

筋肉(muscle)

関: muscle, muscular, muscularis, musculus

「N」

　　[★]

アスパラギン asparagine
窒素(原子、分子)

「Nd」

　　[★] ネオジム neodymium 　

[1] "Entrez Gene: MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)".

[2] Knoepfler PS, Cheng PF, Eisenman RN (2002). "N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation.". Genes Dev. 16 (20): 2699–712. doi:10.1101/gad.1021202. PMID 12381668.

[3] Armstrong BC, Krystal GW (1992). "Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc.". Cell Growth Differ. 3 (6): 385–90. PMID 1419902.

[url_NCBI-4] "MYCN opposite strand/antisense RNA [Homo sapiens]". Entrez Gene Database. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Suenaga Y, Islam SM, Alagu J, Kaneko Y, Kato M, Tanaka Y, Kawana H, Hossain S, Matsumoto D, Yamamoto M, Shoji W, Itami M, Shibata T, Nakamura Y, Ohira M, Haraguchi S, Takatori A, Nakagawara A (2014). "NCYM, a Cis-Antisense Gene of MYCN, Encodes a De Novo Evolved Protein That Inhibits GSK3β Resulting in the Stabilization of MYCN in Human Neuroblastomas". PLoS Genetics 10 (1): e1003996. doi:10.1371/journal.pgen.1003996. PMID 24391509.

[pmid8102299-6] Cheng JM, Hiemstra JL, Schneider SS, Naumova A, Cheung NK, Cohn SL, Diller L, Sapienza C, Brodeur GM (June 1993). "Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas". Nat. Genet. 4 (2): 191–4. doi:10.1038/ng0693-191. PMID 8102299.

[7] Emanuel BS, Balaban G, Boyd JP, Grossman A, Negishi M, Parmiter A, Glick MC (1985). "N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas.". Proc. Natl. Acad. Sci. U.S.A. 82 (11): 3736–40. doi:10.1073/pnas.82.11.3736. PMC 397862. PMID 2582423.

[8] Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984). "Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.". Science 224 (4653): 1121–4. doi:10.1126/science.6719137. PMID 6719137.

[pmid2006410-9] Blackwood EM, Eisenman RN (March 1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science 251 (4998): 1211–7. doi:10.1126/science.2006410. PMID 2006410.

[pmid10229200-10] FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (April 1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc". Oncogene 18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID 10229200.

[pmid19111882-11] Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, Berwanger B, Eilers M (January 2009). "Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma". Cancer Cell 15 (1): 67–78. doi:10.1016/j.ccr.2008.12.005. PMID 19111882.

[12] Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, Eilers M, Shokat KM, Weiss WA (Aug 27, 2014). "Drugging MYCN through an Allosteric Transition in Aurora Kinase A.". Cancer Cell 26: 414–27. doi:10.1016/j.ccr.2014.07.015. PMID 25175806.

匿名

検索

案内

N-myc