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BCR基因产物的结构表征。

Structural characterization of the BCR gene product.

作者信息

Timmons M S, Witte O N

机构信息

Howard Hughes Medical Institute, University of California, Los Angeles 90024-1570.

出版信息

Oncogene. 1989 May;4(5):559-67.

PMID:2657572
Abstract

Chronic myelogenous leukemia (CML) is associated with the reciprocal translocation of a region of chromosome 22 called BCR with the c-abl gene of chromosome 9.5' coding sequences from the BCR gene are spliced in-frame to the second exon of the ABL gene to produce a CML-specific 8.5 kilobase message which encodes the BCR-ABL hybrid protein P210. To definitively identify and characterize the normal BCR gene product, sequences from BCR cDNA clones were used to reconstitute the coding portion of the normal message in retroviral and bacterial transcription vectors. The normal BCR gene product was demonstrated to be a phosphoprotein of 160 kilodaltons by in vitro translation and immunoprecipitation from lysates of NIH3T3 lines expressing BCR retroviruses. Whereas BCR-homologous RNA levels in these cell lines were increased 50 fold, BCR protein levels increased only 2 to 10 fold depending on the presence or absence of BCR-specific 5' and 3' untranslated regions. We observe a kinase activity associated with this protein but we do not observe morphological transformation of NIH3T3 cells as a result of its overproduction.

摘要

慢性粒细胞白血病(CML)与22号染色体上一个名为BCR的区域与9号染色体的c-abl基因发生相互易位有关。BCR基因的5'编码序列与ABL基因的第二个外显子框内拼接,产生一个CML特异性的8.5千碱基信息,该信息编码BCR-ABL融合蛋白P210。为了明确鉴定和表征正常的BCR基因产物,利用BCR cDNA克隆的序列在逆转录病毒和细菌转录载体中重建正常信息的编码部分。通过体外翻译和从表达BCR逆转录病毒的NIH3T3细胞系裂解物中进行免疫沉淀,证明正常的BCR基因产物是一种160千道尔顿的磷蛋白。虽然这些细胞系中BCR同源RNA水平增加了50倍,但BCR蛋白水平仅根据BCR特异性5'和3'非翻译区的存在与否增加了2至10倍。我们观察到与该蛋白相关的激酶活性,但未观察到由于其过量产生导致NIH3T3细胞发生形态转化。

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Structural characterization of the BCR gene product.BCR基因产物的结构表征。
Oncogene. 1989 May;4(5):559-67.
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Common chromatin structures at breakpoint cluster regions may lead to chromosomal translocations found in chronic and acute leukemias.断点簇集区域常见的染色质结构可能导致在慢性和急性白血病中发现的染色体易位。
Hum Genet. 2006 Jun;119(5):479-95. doi: 10.1007/s00439-006-0146-9. Epub 2006 Mar 30.
3
The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain.
Bcr激酶通过磷酸化AF-6并与其PDZ结构域结合来下调Ras信号传导。
Mol Cell Biol. 2003 Jul;23(13):4663-72. doi: 10.1128/MCB.23.13.4663-4672.2003.
4
Amplification of BCR protein associated with oncogenesis in human hepatocellular carcinoma.
Dig Dis Sci. 1997 May;42(5):927-37. doi: 10.1023/a:1018864414582.
5
Bcr and Raf form a complex in vivo via 14-3-3 proteins.在体内,Bcr和Raf通过14-3-3蛋白形成复合物。
EMBO J. 1995 Oct 2;14(19):4839-48. doi: 10.1002/j.1460-2075.1995.tb00165.x.
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Mol Cell Biol. 1995 Feb;15(2):835-42. doi: 10.1128/MCB.15.2.835.
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