文章：

肿瘤蛋白TCL1家族：转化的共激活因子

The TCL1 family of oncoproteins: co-activators of transformation

原文发布日期：2005-08-01

DOI: 10.1038/nrc1672

类型: Review Article

开放获取: 否

要点：

1. The T-cell leukaemia/lymphoma 1 (TCL1) gene family consists of three genes in humans and seven genes in mice and these encode for small, intracellular, β-barrel-shaped proteins. Members of the human TCL1 family are known to bind and augment AKT kinase activity, thereby regulating signal transduction from the environment.
2. Normal expression of TCL1 family members seems to be limited mainly to early embryogenesis, germ cells, specific fetal and adult tissues, and precursor/immature T and B lymphocytes.
3. Dysregulated TCL1-family gene expression in T cells, by chromosome rearrangements, or in B cells, possibly by Epstein–Barr virus infection or aberrant silencing, enhances cell proliferation and survival and leads to cell transformation following a prolonged latency.
4. Transgenic mice that abberantly express TCL1 genes provide unique models of mature human lymphoid malignancies (including T-cell prolymphocytic leukaemia, Burkitt lymphoma, diffuse large B-cell lymphoma, rare follicular lymphoma, and B-cell chronic lymphocytic leukaemia) that have not been seen after other genetic, viral or environmental manipulations.
5. The precise mechanism for TCL1-mediated transformation is not resolved. There are potentially relevant AKT target proteins in the cytosol and possibly the nucleus. To determine how TCL1 proteins cause cancer, it is crucially important that we determine the mechanisms of TCL1-family gene regulation and dysregulation, understand potential AKT-independent effects, discover complementing alterations required for malignancy, and determine transforming activity beyond lymphocytes.

要点翻译：

1. T细胞白血病/淋巴瘤1（TCL1）基因家族在人类中包含三个基因，在小鼠中包含七个基因，这些基因编码小型细胞内β-桶状蛋白。已知人类TCL1家族成员能够结合并增强AKT激酶活性，从而调控来自环境的信号传导。
2. TCL1家族成员的正常表达似乎主要局限于早期胚胎发生、生殖细胞、特定胎儿及成人组织以及前体/未成熟T淋巴细胞和B淋巴细胞。
3. T细胞中因染色体重排或B细胞中可能因EB病毒感染或异常沉默导致的TCL1家族基因表达失调，会增强细胞增殖和存活，并在长潜伏期后引发细胞转化。
4. 异常表达TCL1基因的转基因小鼠为成熟人类淋巴恶性肿瘤（包括T细胞幼淋巴细胞白血病、伯基特淋巴瘤、弥漫性大B细胞淋巴瘤、罕见滤泡性淋巴瘤和B细胞慢性淋巴细胞白血病）提供了独特模型，这些疾病在其他遗传、病毒或环境干预后未曾出现。
5. TCL1介导转化的精确机制尚未明确。细胞质及细胞核中可能存在与AKT相关的靶蛋白。为解析TCL1蛋白如何引发癌症，关键需要明确TCL1家族基因的调控与失调机制，理解其不依赖于AKT的潜在效应，发现恶性转化所需的协同改变，并确定其在淋巴细胞以外的转化活性。

英文摘要：

The T-cell leukaemia/lymphoma 1 (TCL1)-family oncoproteins augment AKT signal transduction and enhance cell proliferation and survival. Chromosome rearrangements, faulty developmental silencing and Epstein–Barr virus infection appear to dysregulate the expression of TCL1-family genes, provoking several important types of lymphocyte cancer. A key role for TCL1 proteins in cell transformation has been established in studies of transgenic mouse models, which develop a unique spectrum of T- and B-cell malignancies. How TCL1 proteins are regulated and dysregulated, how they promote transformation and the potential for therapies modelled on TCL1 interactions have important implications for understanding and treating lymphocyte cancers.

摘要翻译： 

T细胞白血病/淋巴瘤1（TCL1）家族癌蛋白可增强AKT信号转导，促进细胞增殖与存活。染色体易位、发育沉默异常及Epstein–Barr病毒感染均可导致TCL1家族基因表达失调，诱发多种重要的淋巴细胞恶性肿瘤。转基因小鼠模型研究证实TCL1蛋白在细胞转化中发挥关键作用，这些模型会发展为独特的T/B细胞恶性肿瘤谱系。TCL1蛋白的调控与失调机制、其促进转化的方式，以及基于TCL1相互作用的潜在治疗策略，对理解并治疗淋巴细胞癌症具有重要意义。

原文链接：

The TCL1 family of oncoproteins: co-activators of transformation