Kleiber Kai, Strebhardt Klaus, Martin Bernd T
Department of Gynecology and Obstetrics, Medical School, J.W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Anticancer Res. 2007 Jan-Feb;27(1A):55-61.
The LIM-only protein FHL2 (four-and-a-half LIM-domain protein 2) belongs to the FHL protein family of transcriptional cofactors present in various cell lines. FHL2 interacts with a variety of transcription factors known to be involved in tumour development. Furthermore, FHL2 expression is often deregulated in cancer including overexpression and down-regulation in various types of tumours. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. This dual nature of FHL2 is also reflected by the finding that it can function as repressor or activator of transcriptional activity depending on the cell-type. The ability of FHL2 to exert functional diversity lies within its structural composition as a LIM-only protein. LIM-domains are enzymatically inactive protein-to-protein interaction domains, which determine the function of LIM-only proteins as adaptor molecules or scaffolding proteins. By selectively using different LIM-domains for protein-to-protein interactions, FHL2 is capable to interact with a broad spectrum of functionally unrelated proteins, thereby triggering different signalling pathways. In this review, the current knowledge of FHL2 expression in different cancers was summarized and the interaction of FHL2 with transcription factors and other proteins involved in cancer development was examined. Since transcription factors control all fundamental developmental and homeostatic processes, transcriptional cofactors like FHL2 are likely to contribute to human carcinogenesis and are of clinical importance in various forms of cancer.
仅含LIM结构域的蛋白FHL2（四又二分之一LIM结构域蛋白2）属于存在于多种细胞系中的转录辅因子FHL蛋白家族。FHL2与多种已知参与肿瘤发生发展的转录因子相互作用。此外，FHL2的表达在癌症中常常失调，包括在各种类型肿瘤中的过表达和下调。FHL2在癌症中的功能特别引人关注，因为它可能以组织依赖的方式充当癌蛋白或肿瘤抑制因子。FHL2的这种双重性质也体现在以下发现中：根据细胞类型，它可以作为转录活性的抑制因子或激活因子发挥作用。FHL2发挥功能多样性的能力源于其作为仅含LIM结构域蛋白的结构组成。LIM结构域是无酶活性的蛋白质-蛋白质相互作用结构域，它决定了仅含LIM结构域蛋白作为衔接分子或支架蛋白的功能。通过选择性地使用不同的LIM结构域进行蛋白质-蛋白质相互作用，FHL2能够与广泛的功能不相关蛋白相互作用，从而触发不同的信号通路。在本综述中，总结了目前关于FHL2在不同癌症中表达的知识，并研究了FHL2与参与癌症发生发展的转录因子和其他蛋白的相互作用。由于转录因子控制着所有基本的发育和稳态过程，像FHL2这样的转录辅因子很可能在人类致癌过程中发挥作用，并且在各种癌症形式中具有临床重要性。
