Mrvil, a common MRV integration site in BXH2 myeloid leukemias, encodes a protein with homology to a lymphoid-restricted membrane protein Jaw1
Mrvil, a common MRV integration site in BXH2 myeloid leukemias, encodes a protein with homology to a lymphoid-restricted membrane protein Jaw1
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Mrvil 是 BXH2 髓系白血病中常见的 MRV 整合位点，编码与淋巴限制性膜蛋白 Jaw1 同源的蛋白质
DOI：
10.1038/sj.onc.1202419
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发表时间：
1999
期刊：
影响因子：
8
通讯作者：
N. Copeland
中科院分区：
文献类型：
--
作者：
J. Shaughnessy;D. Largaespada;E. Tian;C. Fletcher;B. C. Cho;P. Vyas;N. Jenkins;N. Copeland
共嗜性 MuLV 通过细胞原癌基因或抑癌基因的插入诱变诱导 BXH2 小鼠患骨髓性白血病。因此，可以通过病毒标记将疾病基因识别为 BXH2 白血病中病毒整合的常见位点。先前的研究表明，BXH2 白血病中常见的整合位点是 Nf1 抑癌基因。出乎意料的是，Nf1 上大约一半的病毒整合代表了一种以前未被发现的有缺陷的非共亲性病毒，称为 MRV。由于 BXH2 白血病中编码原癌基因的其他常见整合位点包含共嗜性病毒而不是 MRV 病毒，因此推测 MRV 病毒可能选择性地靶向肿瘤抑制基因。为了确定情况是否如此，我们对 21 例 MRV 阳性 BXH2 白血病进行了筛查，寻找新的 MRV 共同整合位点。在两种白血病中，一个新位点 Mrvi1 被 MRV 破坏。在 205 例嗜食性病毒阳性白血病中，嗜食性病毒并未破坏 Mrvi1，这表明 Mrvi1 是 MRV 的特异性靶标。 Mrvi1 编码一种与 Jaw1 同源的新型蛋白质，Jaw1 是一种定位于内质网的淋巴限制性 II 型膜蛋白。 MRV 整合发生在两个不同使用的启动子之间的基因 5' 端。在造血细胞内，Mrvi1 表达仅限于巨核细胞和一些骨髓性白血病。与在淋巴分化过程中下调的 Jaw1 一样，Mrv1 在 BXH2 白血病的单核细胞分化过程中也下调。总而言之，这些数据表明，Mrvi1 上的 MRV 整合通过改变对骨髓细胞生长和/或分化重要的基因的表达来诱导骨髓白血病。测试 Mrvi1 是否是肿瘤抑制基因的实验正在进行中。
Ecotropic MuLVs induce myeloid leukemia in BXH2 mice by insertional mutagenesis of cellular proto-oncogenes or tumor suppressor genes. Disease genes can thus be identified by viral tagging as common sites of viral integration in BXH2 leukemias. Previous studies showed that a frequent common integration site in BXH2 leukemias is the Nf1 tumor suppressor gene. Unexpectedly, about half of the viral integrations at Nf1 represented a previously undiscovered defective nonecotropic virus, termed MRV. Because other common integration sites in BXH2 leukemias encoding proto-oncogenes contain ecotropic rather than MRV viruses, it has been speculated that MRV viruses may selectively target tumor suppressor genes. To determine if this were the case, 21 MRV-positive BXH2 leukemias were screened for new MRV common integration sites. One new site, Mrvi1 was identified that was disrupted by MRV in two of the leukemias. Ecotropic virus did not disrupt Mrvi1 in 205 ecotropic virus-positive leukemias, suggesting that Mrvi1 is specifically targeted by MRV. Mrvi1 encodes a novel protein with homology to Jaw1, a lymphoid restricted type II membrane protein that localizes to the endoplasmic reticulum. MRV integration occurs at the 5′ end of the gene between two differentially used promoters. Within hematopoietic cells, Mrvi1 expression is restricted to megakaryocytes and some myeloid leukemias. Like Jaw1, which is downregulated during lymphoid differentiation, Mrv1 is downregulated during monocytic differentiation of BXH2 leukemias. Taken together, these data suggest that MRV integration at Mrvi1 induces myeloid leukemia by altering the expression of a gene important for myeloid cell growth and/or differentiation. Experiments are in progress to test whether Mrvi1 is a tumor suppressor gene.
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胃腺癌中 11 号染色体杂合性缺失。
DOI：
--
发表时间：
1996
期刊：
Cancer research.
影响因子：
--
作者：
Baffa,R;Negrini,M;Mandes,B;Rugge,M;Ranzani,GN;Hirohashi,S;Croce,CM
通讯作者：
Croce,CM
影响因子：
56.9
作者：
ROGERS, S;WELLS, R;RECHSTEINER, M
通讯作者：
RECHSTEINER, M
影响因子：
56.9
作者：
COPELAND, NG;JENKINS, NA;LANDER, ES
通讯作者：
LANDER, ES
影响因子：
56.9
作者：
SUDHOF, TC;CZERNIK, AJ;GREENGARD, P
通讯作者：
GREENGARD, P