Department of Chemistry, 3359 Mississauga Road North, South Building, Rm 4046, University of Toronto, Mississauga, ON L5L 1C6.
Biochem Cell Biol. 2009 Dec;87(6):825-33. doi: 10.1139/o09-044.
Signal transducer and activator of transcription protein 3 (STAT3) is a latent cytosolic transcription factor that is widely recognized as being a master regulator of the cellular functions that lead to the cancer phenotype. Constitutively activated STAT3 protein activity is routinely observed in human cancers, promoting uncontrolled cell proliferation and suppressing apoptosis. Until relatively recently, inhibition of STAT3 transcriptional activity was achieved indirectly via suppression of upstream kinase activators and extracellular cytokine and (or) growth factor stimuli. However, activated STAT3 forms transcriptionally functional STAT3-STAT3 dimers, providing a valid juncture for targeted downstream molecular inhibition. STAT3's prominent role in cancer has seen a decade of innovative and novel approaches to targeting constitutively active STAT3 protein-protein complexes. This mini-review outlines the progress made towards identifying molecular agents capable of silencing aberrant STAT3 signalling through the disruption of STAT3 complexation events.
信号转导和转录激活因子 3（STAT3）是一种潜在的胞质转录因子，被广泛认为是导致癌症表型的细胞功能的主要调节因子。在人类癌症中，通常观察到组成性激活的 STAT3 蛋白活性，促进不受控制的细胞增殖并抑制细胞凋亡。直到最近，STAT3 转录活性的抑制还是通过抑制上游激酶激活剂以及细胞外细胞因子和（或）生长因子刺激来间接实现的。然而，激活的 STAT3 形成转录功能上的 STAT3-STAT3 二聚体，为靶向下游分子抑制提供了有效的结合点。STAT3 在癌症中的突出作用使得人们在过去十年中创新性地开发了针对组成性激活的 STAT3 蛋白-蛋白复合物的新方法。这篇小型综述概述了在鉴定能够通过破坏 STAT3 复合物形成事件来沉默异常 STAT3 信号的分子药物方面所取得的进展。
