Identification of a novel splice variant of the human anti-apoptosis gene survivin

Identification of a novel splice variant of the human anti-apoptosis gene survivin
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DOI:
10.1016/j.bbrc.2003.12.178
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发表时间:
2004-02-13
影响因子:
3.1
通讯作者:
Inuzuka, M
Inuzuka, M
中科院分区:
生物学4区
文献类型:
--
作者:
Badran, A;Yoshida, A;Inuzuka, M

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Survivin是凋亡抑制蛋白(inhibitor of apoptosis protein,IAP)家族的一个新成员,在多种肿瘤中表达,而在分化正常的组织中不表达。在本研究中,我们描述了一种新的选择性剪接生存素转录,命名为生存素-3B的鉴定。它包含5个外显子,包括新的外显子3B,其衍生自内含子3的165-bp长的部分。在新外显子313内获得新的框内TGA终止密码子导致363个核苷酸的开放阅读框(ORF),预测截短的120个氨基酸的蛋白质。检测人结肠癌和胃腺癌细胞系以及骨髓增生异常综合征(MDS)和急性髓性白血病(AML)患者单个核细胞中Survivin-3B的表达。Survivin-3B含有一个杆状病毒IAP重复序列(BIR),它对细胞凋亡的抑制至关重要。然而,它缺乏一个羧基端卷曲螺旋结构域,这表明生存素-3B可能不与G2/M期。这些数据表明Survivin-3B的功能可能不同于常规Survivin。(C)2003年爱思唯尔公司All rights reserved.
Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissues. In the present study, we describe the identification of a novel alternatively spliced survivin transcript, designated as survivin-3B. It comprises 5 exons including novel exon 3B derived from a 165-bp long portion of intron 3. Acquisition of a new in-frame TGA stop codon within the novel exon 313 results in an open reading frame (ORF) of 363 nucleotides, predicting a truncated 120 amino acid protein. Expression of survivin-3B was detected in human colon and gastric adenocarcinoma cell lines as well as mononuclear cells prepared from patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Survivin-3B contains a single baculovirus IAP repeat (BIR), which is critical for apoptosis inhibition. However, it lacks a carboxyl-terminal coiled-coil domain, suggesting that survivin-3B may not be associated with G2/M phase. These data indicate that the function of survivin-3B may be different from that of regular survivin. (C) 2003 Elsevier Inc. All rights reserved.