Ellenrieder Volker
Signal Transduction Laboratory, Internal Medicine, Department of Gastroenterology and Endocrinology, University of Marburg, Marburg, Germany.
Anticancer Res. 2008 May-Jun;28(3A):1531-9.
Transforming growth factor beta (TGFbeta) controls vital cellular functions through its ability to regulate gene expression. TGFbeta binding to its transmembrane receptor kinases initiates distinct intracellular signalling cascades including the Smad signalling and transcription factors and also Smad-independent pathways. In normal epithelial cells, TGFbeta stimulation induces a cytostatic program which includes the transcriptional repression of the c-Myc oncogene and the later induction of the cell cycle inhibitors p15(INK4b) and p21(Cip1). During carcinogenesis, however, many tumor cells lose their ability to respond to TGFbeta with growth inhibition, and instead, activate genes involved in cell proliferation, invasion and metastasis. Strong efforts have been made during recent years to characterize Smad-mediated transcriptional processes and to identify those TGFbeta-regulated transcription factors that control gene expression independent of the Smads. These studies have led to the identification of a novel family of TGFbeta-inducible Sp1/KLF-(Krüppel-like factors) like transcription factors (KLF10 and KLF11) which play remarkable roles in TGFbeta mediated cell growth control and differentiation. In this article, the current knowledge on the peculiar roles of Sp1/KLF-like proteins in Smad dependent and -independent gene regulation initiated by TGFbeta, are summarized.
转化生长因子β（TGFβ）通过其调节基因表达的能力来控制重要的细胞功能。TGFβ与其跨膜受体激酶结合会启动不同的细胞内信号级联反应，包括Smad信号传导和转录因子以及非Smad依赖性途径。在正常上皮细胞中，TGFβ刺激会诱导一种细胞静止程序，其中包括c-Myc癌基因的转录抑制以及随后细胞周期抑制剂p15（INK4b）和p21（Cip1）的诱导。然而，在致癌过程中，许多肿瘤细胞失去了对TGFβ生长抑制的反应能力，反而激活了参与细胞增殖、侵袭和转移的基因。近年来，人们付出了巨大努力来表征Smad介导的转录过程，并确定那些独立于Smads控制基因表达的TGFβ调节转录因子。这些研究导致鉴定出一个新的TGFβ诱导的Sp1/KLF-（类Krüppel样因子）样转录因子家族（KLF10和KLF11），它们在TGFβ介导的细胞生长控制和分化中发挥着重要作用。在本文中，总结了关于Sp1/KLF样蛋白在TGFβ引发的Smad依赖性和非依赖性基因调控中的特殊作用的当前知识。
