Regulation of myocardin-related transcriptional coactivators through cofactor interactions in differentiation and cancer
Regulation of myocardin-related transcriptional coactivators through cofactor interactions in differentiation and cancer
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DOI：
10.4161/cc.8.16.9398
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发表时间：
2009-08-15
期刊：
影响因子：
4.3
通讯作者：
Grosse, Robert
中科院分区：
文献类型：
--
作者：
Brandt, Dominique T.;Xu, Jianming;Grosse, Robert
转录信号网络通过转录因子与辅因子子集的多重相互作用进行编排和微调，从而组装多蛋白复合物以负向或正向平衡转录输出。这些机制解释了靶基因的巨大多样性，也解释了通过单一转录因子（例如SRF）对时间和组织特异性基因的调控。心肌素相关转录因子 (MRTF) 是备受关注的 SRF 共激活因子家族之一。 MRTF 本身是通过与越来越多的辅助因子和转录调节因子的相互作用来控制的。我们最近发现了 SCAI（癌细胞侵袭抑制剂），它可以与 MAL (MRTF-A) 结合，通过调节 β1-整合素表达和功能来调节侵袭性癌细胞迁移。然而，SCAI 可能具有额外的功能，具体取决于组织环境和信号传导程序。有趣的是，SCAI 不仅抑制 MRTF-A，还可以调节其他 MRTF 的活性，例如心肌素或致癌的 OTT-MAL 融合蛋白。因此，SCAI 可能在非常不同的条件下发挥作用，例如在癌症进展、发育或细胞分化期间。
Transcriptional signaling networks are orchestrated and fine-tuned through multiple interactions of transcription factors with subsets of cofactors thereby assembling multiprotein complexes to negatively or positively balance transcriptional output. These mechanisms account for the large diversity of target genes but also for time and tissue specific gene regulations through single transcription factors such as SRF. One family of SRF coactivators that has attracted much attention is represented by the myocardin-related transcription factors (MRTFs). MRTFs themselves are controlled through interactions with a growing number of cofactors and transcriptional regulators. We recently identified SCAI (suppressor of cancer cell invasion), which can associate with MAL (MRTF-A) to modulate invasive cancer cell migration through regulation of beta 1-integrin expression and function. However, SCAI is likely to have additional functions depending on the tissue environment and signaling program. Interestingly, SCAI not only inhibits MRTF-A but can also regulate the activities of other MRTFs such as myocardin, or the oncogenic OTT-MAL fusion protein. Thus, SCAI may act in very different conditions such as during cancer progression, development or cell differentiation.