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在携带t(1;19)易位的人类白血病中，与E2A融合可将Pbx1同源结构域蛋白转化为组成型转录激活因子。

Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation.

作者信息

Lu Q, Wright D D, Kamps M P

机构信息

Department of Chemistry, University of California, San Diego, La Jolla 92093.

出版信息

Mol Cell Biol. 1994 Jun;14(6):3938-48. doi: 10.1128/mcb.14.6.3938-3948.1994.

DOI:10.1128/mcb.14.6.3938-3948.1994
PMID:7910944
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC358760/
Abstract

E2A-PBX1 is a chimeric gene formed by the t(1;19)(q23;p13.3) chromosomal translocation of pediatric pre-B-cell leukemia. The E2A-Pbx1 fusion protein contains sequences encoding the transactivation domain of E2A joined to a majority of the Pbx1 protein, which contains a novel homeodomain. Earlier, we found that expression of E2A-Pbx1 causes malignant transformation of NIH 3T3 fibroblasts and induces myeloid leukemia in mice. Here we demonstrate that the homeodomains encoded by PBX1, as well as by the highly related PBX2 and PBX3 genes, bind the DNA sequence ATCAATCAA. E2A-Pbx1 strongly activates transcription in vivo through this motif, while Pbx1 does not. This finding suggests that E2A-Pbx1 transforms cells by constitutively activating transcription of genes regulated by Pbx1 or by other members of the Pbx protein family.

摘要

E2A-PBX1是一种由儿童前B细胞白血病的t(1;19)(q23;p13.3)染色体易位形成的嵌合基因。E2A-Pbx1融合蛋白包含编码E2A反式激活结构域的序列，该序列与大部分Pbx1蛋白相连，Pbx1蛋白含有一个新的同源结构域。此前，我们发现E2A-Pbx1的表达会导致NIH 3T3成纤维细胞发生恶性转化，并在小鼠中诱导髓系白血病。在此我们证明，PBX1以及高度相关的PBX2和PBX3基因编码的同源结构域与DNA序列ATCAATCAA结合。E2A-Pbx1通过该基序在体内强烈激活转录，而Pbx1则不能。这一发现表明，E2A-Pbx1通过组成性激活由Pbx1或Pbx蛋白家族其他成员调控的基因转录来转化细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/85149a6a0cd2/molcellb00006-0427-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/cd39e02d47df/molcellb00006-0425-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/7108cd5eba9b/molcellb00006-0426-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/85149a6a0cd2/molcellb00006-0427-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/cd39e02d47df/molcellb00006-0425-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/7108cd5eba9b/molcellb00006-0426-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6302/358760/85149a6a0cd2/molcellb00006-0427-a.jpg

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1
Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation.在携带t(1;19)易位的人类白血病中，与E2A融合可将Pbx1同源结构域蛋白转化为组成型转录激活因子。
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本文引用的文献

1
Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements.不同病毒诱导增强子元件之间的转录协同作用机制。
Cell. 1993 Sep 10;74(5):887-98. doi: 10.1016/0092-8674(93)90468-6.
2
Functional domains of the Drosophila Engrailed protein.果蝇成对规则蛋白的功能结构域。
EMBO J. 1993 Jul;12(7):2723-33. doi: 10.1002/j.1460-2075.1993.tb05934.x.
3
Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia.在前B细胞急性淋巴细胞白血病中，Pbx1通过获得E2A的N端区域而转变为转录激活因子。
胆汁酸-FXR-FGF15/19 信号轴的分子基础。
Int J Mol Sci. 2022 May 27;23(11):6046. doi: 10.3390/ijms23116046.
4
functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the gene family.作为结直肠癌中一种潜在的新型癌基因促进因子发挥作用：对该基因家族的综合分析
Am J Cancer Res. 2022 Feb 15;12(2):585-600. eCollection 2022.
5
Incidence and Prognostic Impact of TCF3-PBX1 Fusion in Childhood Acute Lymphoblastic Leukemia: A Single Centre Experience.TCF3-PBX1融合基因在儿童急性淋巴细胞白血病中的发生率及预后影响：单中心经验
Indian J Hematol Blood Transfus. 2022 Jan;38(1):164-168. doi: 10.1007/s12288-021-01452-7. Epub 2021 May 22.
6
PBX1: a key character of the hallmarks of cancer.PBX1：癌症特征的关键特征之一。
J Mol Med (Berl). 2021 Dec;99(12):1667-1680. doi: 10.1007/s00109-021-02139-2. Epub 2021 Sep 16.
7
A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates.Hox-TALE 调控回路在脊椎动物中对神经嵴的模式形成具有保守性。
Nat Commun. 2019 Mar 13;10(1):1189. doi: 10.1038/s41467-019-09197-8.
8
Molecular processes involved in B cell acute lymphoblastic leukaemia.B 细胞急性淋巴细胞白血病涉及的分子过程。
Cell Mol Life Sci. 2018 Feb;75(3):417-446. doi: 10.1007/s00018-017-2620-z. Epub 2017 Aug 17.
9
New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins.AML1-ETO和E2A融合蛋白转录及白血病发生机制的新见解
Front Biol (Beijing). 2016 Aug;11(4):285-304. doi: 10.1007/s11515-016-1415-1. Epub 2016 Sep 3.
10
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Leukemia. 2015 Feb;29(2):304-11. doi: 10.1038/leu.2014.210. Epub 2014 Jul 3.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6061-5. doi: 10.1073/pnas.90.13.6061.
4
extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1.额外齿（extradenticle）是同源异型基因活性的调节因子，是含同源异型框的人类原癌基因pbx1的同源物。
Cell. 1993 Sep 24;74(6):1101-12. doi: 10.1016/0092-8674(93)90731-5.
5
Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice.嵌合型同源盒基因E2A-PBX1在转基因小鼠中诱导增殖、凋亡及恶性淋巴瘤。
Cell. 1993 Sep 10;74(5):833-43. doi: 10.1016/0092-8674(93)90463-z.
6
Transcriptional repression by the Drosophila even-skipped protein: definition of a minimal repression domain.果蝇even-skipped蛋白介导的转录抑制：最小抑制结构域的定义
Genes Dev. 1993 Mar;7(3):491-503. doi: 10.1101/gad.7.3.491.
7
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Mol Cell Biol. 1993 Jan;13(1):351-7. doi: 10.1128/mcb.13.1.351-357.1993.
8
Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.在哺乳动物细胞中表达氯霉素乙酰转移酶的重组基因组。
Mol Cell Biol. 1982 Sep;2(9):1044-51. doi: 10.1128/mcb.2.9.1044-1051.1982.
9
Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila.控制发育的基因间的结构关系：果蝇触角足、超双胸和腹沟基因座之间的序列同源性
Proc Natl Acad Sci U S A. 1984 Jul;81(13):4115-9. doi: 10.1073/pnas.81.13.4115.
10
A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans.果蝇同源异型基因中的一个同源蛋白质编码序列及其在其他后生动物中的保守性。
Cell. 1984 Jun;37(2):403-8. doi: 10.1016/0092-8674(84)90370-2.