Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions.
Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions.
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发表时间：
1995-05
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通讯作者：
G. Neale;S. Mao;D. Parham;K. Murti;R. Goorha
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作者：
G. Neale;S. Mao;D. Parham;K. Murti;R. Goorha
Rhombotin-2（RBTN-2）是一种LIM结构域蛋白，除胸腺细胞外，在胎儿发育过程中广泛表达。虽然RBTN-2对正常红细胞生成至关重要，但RBTN-2在T淋巴细胞中的异位表达导致T细胞增殖和白血病发生。因此，虽然RBTN-2的增殖功能已在T细胞中建立，但其在红细胞生成中的作用及其在其他组织中的功能都是未知的。我们研究了RBTN-2在正常和恶性细胞中的表达和定位。与胎儿发育相似，除结肠和胸腺细胞外，在所有正常成人组织中均检测到RBTN-2 RNA。在所有原发性肿瘤和肿瘤细胞系中均未检测到RBTN-2 RNA，表明RBTN-2表达在增殖细胞中并非普遍存在。使用多克隆抗血清，RBTN-2主要在人造血细胞的细胞核中检测到。值得注意的是，具有RBTN-2基因座破坏的人白血病T细胞和来自具有RBTN-2强制表达的转基因小鼠的胸腺细胞显示出相似的RBTN-2蛋白的核定位，这与RBTN-2在T细胞增殖中充当转录调节因子的概念一致。令人惊讶的是，在正常组织中，RBTN-2显示出与金属硫蛋白-1惊人相似的分布，具有细胞核和细胞质定位，这表明RBTN-2可能参与急性期反应。事实上，类似于金属硫蛋白-1，RBTN-2 mRNA在暴露于锌的小鼠胸腺细胞和用佛波酯12-O-十四酰基佛波醇-13-乙酸酯处理的人胸腺细胞中诱导。由于LIM结构域允许多个蛋白质伴侣的结合，RBTN-2的特异性功能可能取决于通过与不同辅因子相互作用的亚细胞隔离。因此，除了在红细胞生成和T细胞白血病中的作用外，RBTN-2还可能参与急性期反应。
Rhombotin-2 (RBTN-2) is a LIM domain protein that, with the exception of thymocytes, is widely expressed during fetal development. Although RBTN-2 is crucial for normal erythropoiesis, the ectopic expression of RBTN-2 in T lymphocytes results in T-cell proliferation and leukemogenesis. Thus, while a proliferative function for RBTN-2 has been established in T-cells, neither its role in erythropoiesis nor its function(s) in other tissues are known. We have examined the expression and location of RBTN-2 in normal and malignant cells. Similar to fetal development, RBTN-2 RNA was detected in all normal adult tissues tested with the exception of colon and thymocytes. RBTN-2 RNA was not detected in all primary tumors and tumor cell lines, indicating RBTN-2 expression is not ubiquitous in proliferating cells. Using polyclonal antisera, RBTN-2 was detected predominantly in the nucleus of human hematopoietic cells. Significantly, human leukemic T cells with disruption of the RBTN-2 locus and thymocytes from transgenic mice with enforced expression of RBTN-2 showed similar nuclear location of RBTN-2 protein, consistent with the notion that RBTN-2 acts as a transcriptional regulator in T-cell proliferation. Surprisingly, in normal tissues, RBTN-2 showed a strikingly similar distribution to that of metallothionein-1, having both nuclear and cytoplasmic localization that suggested that RBTN-2 may be involved in the acute phase response. Indeed, similar to metallothionein-1, RBTN-2 mRNA was induced in thymocytes of mice exposed to zinc and in human thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Since the LIM domain permits binding of multiple protein partners, the specific function of RBTN-2 may depend upon subcellular sequestration through interaction with different cofactors. Thus, in addition to its roles in erythropoiesis and T-cell leukemia, RBTN-2 may also be involved in the acute phase response.