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{{NoteTA|G1=LS}}
{{Infobox_gene}}

'''CCAAT/增强子结合蛋白α'''，简称'''C/EBP-α'''或'''CEBPA'''，化学式为：C1656H2581O494N491S9<ref>{{Cite web |title=Expasy - ProtParam |url=https://web.expasy.org/cgi-bin/protparam/protparam_bis.cgi?P49715@1-358@ |website=web.expasy.org |access-date=2026-01-24}}</ref>，是一种由人类''CEBPA''[[基因]]编码的[[蛋白质]]。<ref name="pmid1535333">{{cite journal |vauthors=Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J |date=July 1992 |title=Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF) |journal=Genomics |volume=13 |issue=2 |pages=293–300 |doi=10.1016/0888-7543(92)90245-N |pmid=1535333}}</ref><ref name="pmid1840554">{{cite journal |vauthors=Cao Z, Umek RM, McKnight SL |date=October 1991 |title=Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells |journal=Genes Dev |volume=5 |issue=9 |pages=1538–52 |doi=10.1101/gad.5.9.1538 |pmid=1840554 |doi-access=free}}</ref>CEBPA是参与某些[[血细胞]]分化的[[转录因子]]。<ref>{{Cite web |date=April 20, 2016 |title=CEBPA |url=https://ghr.nlm.nih.gov/gene/CEBPA |access-date=April 25, 2016 |website=Genetics Home Reference }}</ref>有关基因增强子中的CCAAT[[结构基序]]和CCAAT/[[強化子|增强子]]结合蛋白的详细信息，请参见特定[[CCAAT/增强子结合蛋白|页面]]。

== 功能 ==
这种[[内含子|无内含子]]基因编码的蛋白质是一种[[BZIP结构域|bZIP]]转录因子，它可以作为同源[[二聚体]]与某些[[启动子]]和基因增强子结合。它还可以与相关蛋白[[CEBPB|C/EBP-β]]和[[CEBPG|C/EBP-γ]]以及不同的转录因子如[[转录因子c-Jun|c-Jun]]形成异二聚体。编码的蛋白质是[[脂肪细胞生成]]和这些细胞中[[脂质]]积累以及[[肝脏]]中[[葡萄糖]]和脂质代谢的关键调节因子。<ref name="Olofsson2008">{{cite journal |vauthors=Olofsson LE, Orho-Melander M, William-Olsson L, Sjöholm K, Sjöström L, Groop L, Carlsson B, Carlsson LM, Olsson B |date=1 December 2009 |title=CCAAT/enhancer binding protein alpha (C/EBPalpha) in adipose tissue regulates genes in lipid and glucose metabolism and a genetic variation in C/EBPalpha is associated with serum levels of triglycerides |journal=[[The Journal of Clinical Endocrinology & Metabolism]] |volume=93 |issue=12 |pages=4880–4886 |doi=10.1210/jc.2008-0574 |pmid=18765514 |doi-access=free}}</ref>该蛋白质已被证明与启动子结合并调节编码[[瘦蛋白]]的基因的表达，[[瘦蛋白]]是一种在体重稳态中起重要作用的蛋白质。此外，编码的蛋白质可以与[[周期蛋白依赖性激酶2|CDK2]]和[[周期蛋白依赖性激酶4|CDK4]]相互作用，从而抑制这些[[激酶]]并导致培养的细胞停止分裂。<ref>{{cite web |title=Entrez Gene: CEBPA CCAAT/enhancer binding protein (C/EBP), alpha |url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1050 }}</ref>此外，CEBPA对[[骨髓細胞|骨髓]]谱系定型至关重要，因此对于正常成熟[[粒细胞]]的形成和异常[[急性骨髓性白血病]]的发展都是必需的。<ref>{{cite journal |vauthors=Ohlsson E, Schuster MB, Hasemann M, Porse BT |date=Apr 2016 |title=The multifaceted functions of C/EBPalpha in normal and malignant haematopoiesis |journal=Leukemia |volume=30 |issue=4 |pages=767–75 |doi=10.1038/leu.2015.324 |pmid=26601784 |s2cid=24767947}}</ref>

== 常见突变 ==
CEBPA突变可分为两大类。一类突变通过改变其COOH末端碱性亮氨酸拉链结构域来阻止CEBPA的DNA结合。另一类突变破坏了CEBPA的NH2末端的翻译。 CEBPA突变导致CEBPA活性降低，有助于骨髓前体的转化。<ref name=":0">{{cite journal |display-authors=etal |vauthors=Lin LI, Chen CY, Lin DT, Tsay W, Tang JL, Yeh YC |year=2005 |title="Characterization of CEBPA mutations in acute myeloid leukemia " most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells |journal=Clin Cancer Res |volume=11 |issue=4 |pages=1372–9 |doi=10.1158/1078-0432.ccr-04-1816 |pmid=15746035 |doi-access=free}}</ref>

== 相互作用 ==
CEBPA已被证明与[[周期蛋白依赖性激酶2]][[蛋白質相互作用|相互作用]]<ref name="pmid11684017">{{cite journal |vauthors=Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ, Timchenko NA |date=October 2001 |title=C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4 |journal=Mol. Cell |volume=8 |issue=4 |pages=817–28 |doi=10.1016/S1097-2765(01)00366-5 |pmid=11684017 |doi-access=free}}</ref>和[[周期蛋白依赖性激酶4]]。<ref name="pmid11684017" />

== 临床意义 ==
CEBPA的突变已被证明与成人和儿童[[急性骨髓性白血病]]患者的良好结果有关。<ref name="pmid19304957">{{cite journal |vauthors=Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Radich JP, Meshinchi S |date=June 2009 |title=Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group |journal=Blood |volume=113 |issue=26 |pages=6558–66 |doi=10.1182/blood-2008-10-184747 |pmc=2943755 |pmid=19304957}}</ref>

=== 在急性骨髓性白血病中的意义 ===
急性骨髓性白血病的特征在于造血[[祖細胞|祖细胞]]的遗传异常。这包括原始细胞的过度增殖，以及阻止[[粒细胞]]的[[造血作用|造血]]。已经表明，抑制CEBPA表达和阻断CEBPA会阻止骨髓祖细胞的分化。出于这个原因，CEBPA在粒细胞分化过程中的作用和CEBPA作为[[肿瘤抑制基因]]的作用在急性髓细胞白血病的预后中至关重要。<ref>{{cite journal |display-authors=etal |vauthors=Lin TC, Hou HA, Chou WC, Ou DL, Yu SL, Tien HF |year=2011 |title=CEBPA methylation as a prognostic biomarker in patients with ''de novo'' acute myeloid leukemia |journal=Leukemia |volume=25 |issue=1 |pages=32–40 |doi=10.1038/leu.2010.222 |pmid=20927134 |doi-access=free}}</ref>

=== CEBPA突变的预后意义 ===
CEBPA在未成熟粒细胞的分化中非常重要。CEBPA基因的突变已被证明在急性骨髓性白血病患者的[[白血病]]发生和预后中起关键作用。在最近的研究中，在7%到15%的急性骨髓性白血病患者中发现了CEBPA突变。在这些急性骨髓性白血病患者中看到的三种不同类型的突变包括种系N末端突变、N末端[[框移突變|框移突变]]和C末端突变。这些突变最常见于急性骨髓性白血病M1或M2。许多报道将CEBPA突变与急性骨髓细胞白血病的良好结果联系起来。这是因为这些突变可能会导致这些患者的[[细胞分化|分化]]停滞。有CEBPA突变的患者比没有突变的患者有更长的缓解持续时间和生存时间。<ref name=":0" />因此，CEBPA突变的存在与疾病进展的更有利过程直接相关。<ref>El-Sharnouby JA, Ahmed LM, Taha AM, Kamal O. Prognostic significance of CEBPA mutations and BAALC expression in acute myeloid leukemia Egyptian patients with normal karyotype. Egypt J Immunol. 2010;15:131–143.</ref>

=== 在实体瘤中的意义 ===
最近显示，CEBPA远端启动子区域的[[表观遗传]]修饰导致[[胰腺癌]]细胞、[[肺癌]]和头颈部[[鳞状细胞癌]]中CEBPA表达[[上调和下调|下调]]。<ref>{{cite journal |vauthors=Tada Y, Brena RM, Hackanson B, Morrison C, Otterson GA, Plass C |year=2006 |title=Epigenetic modulation of tumor suppressor CCAAT/enhancer binding protein alpha activity in lung cancer |url=https://archive.org/details/sim_journal-of-the-national-cancer-institute_2006-03-15_98_6/page/396 |journal=J Natl Cancer Inst |volume=98 |issue=6 |pages=396–406 |doi=10.1093/jnci/djj093 |pmid=16537832 |doi-access=free}}</ref><ref>{{cite journal |display-authors=etal |vauthors=Bennett KL, Hackanson B, Smith LT, Morrison CD, Lang JC, Schuller DE |year=2007 |title=Tumor suppressor activity of CCAAT/enhancer binding protein alpha is epigenetically down-regulated in head and neck squamous cell carcinoma |url=https://archive.org/details/sim_cancer-research_2007-05-15_67_10/page/n140 |journal=Cancer Res |volume=67 |issue=10 |pages=4657–4664 |doi=10.1158/0008-5472.can-06-4793 |pmid=17510391 |doi-access=free}}</ref>

=== CEBPA的甲基化作为急性骨髓性白血病患者的预后生物标记 ===
最近的一项研究发现，较高水平的CEBPA[[甲基化]]与治疗反应成正比。完全反应率与CEBPA甲基化水平成比例增加。出于这个原因，有人提出CEBPA的甲基化可能是急性髓细胞白血病[[预后]]中非常有用的[[生物标记]]。<ref>{{cite journal |display-authors=etal |vauthors=Lin TC, Hou HA, Chou WC, Ou DL, Yu SL, Tien HF |year=2011 |title=CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia |journal=Leukemia |volume=25 |issue=1 |pages=32–40 |doi=10.1038/leu.2010.222 |pmid=20927134 |doi-access=free}}</ref>

== 参考文献 ==
{{reflist}}

== 阅读 ==
{{refbegin|2}}
* {{cite journal |vauthors=Sladek FM, Darnell JE |year=1992 |title=Mechanisms of liver-specific gene expression. |journal=Curr. Opin. Genet. Dev. |volume=2 |issue=2 |pages=256–9 |doi=10.1016/S0959-437X(05)80282-5 |pmid=1638120}}
* {{cite journal |vauthors=Marcucci G, Mrózek K, Bloomfield CD |year=2005 |title=Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. |journal=Curr. Opin. Hematol. |volume=12 |issue=1 |pages=68–75 |doi=10.1097/01.moh.0000149608.29685.d1 |pmid=15604894 |s2cid=6183391}}
* {{cite journal |vauthors=Leroy H, Roumier C, Huyghe P, Biggio V, Fenaux P, Preudhomme C |date=March 2005 |title=CEBPA point mutations in hematological malignancies |journal=Leukemia |volume=19 |issue=3 |pages=329–34 |doi=10.1038/sj.leu.2403614 |pmid=15674366 |doi-access=free}}
{{refend}}

== 外部链接 ==

* {{UCSC gene info|CEBPA}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cebpa-aml GeneReviews/NIH/NCBI/UW entry on Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA] {{Wayback|url=https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cebpa-aml |date=20210827204536 }}
* {{MeshName|CEBPA+protein,+human}}
{{PDB Gallery|geneid=1050}}{{转录因子与细胞内受体|g1}}

[[Category:转录因子]]

CEBPA - 版本历史

imported>曦城星月 来自 2026年1月24日 (六) 11:56

imported>曦城星月来自 2026年1月24日 (六) 11:56