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首页> 外文期刊>Molecular and Cellular Biology >TBP Is Differentially Regulated by c-Jun N-Terminal Kinase 1 (JNK1) and JNK2 through Elk-1, Controlling c-Jun Expression and Cell Proliferation
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TBP Is Differentially Regulated by c-Jun N-Terminal Kinase 1 (JNK1) and JNK2 through Elk-1, Controlling c-Jun Expression and Cell Proliferation

机译：TBP由c-Jun N末端激酶1（JNK1）和JNK2通过Elk-1差异调节，控制c-Jun的表达和细胞增殖

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摘要

Emerging evidence supports the idea that the c-Jun N-terminal kinases (JNKs) possess overlapping but distinct functions. The potential roles of the ubiquitously expressed JNK1 and JNK2 in regulating expression of the central transcription initiation factor, TATA-binding protein (TBP), were examined. Relative to wild-type fibroblasts, TBP was decreased in Jnk1?/? cells and increased in Jnk2?/? cells. Similarly, reduction of JNK1 in human hepatoma cells decreased TBP expression, whereas reduction of JNK2 enhanced it. JNK-mediated regulation of TBP expression occurs at the transcriptional level through their ability to target Elk-1, which directly regulates the TBP promoter in response to epidermal growth factor stimulation. JNK1 increases, whereas JNK2 decreases, the phosphorylation state of Elk-1, which differentially affects Elk-1 occupancy at a defined site within the TBP promoter. These JNK-mediated alterations in TBP expression, alone, serve to regulate c-Jun expression and fibroblast proliferation rates. These studies uncovered several new molecular events that distinguish the functions of JNK1 and JNK2 that are critical for their regulation of cellular proliferation.
机译：新兴证据支持c-Jun N末端激酶（JNK）具有重叠但截然不同的功能这一观点。检查了普遍表达的JNK1和JNK2在调节中央转录起始因子TATA结合蛋白（TBP）表达中的潜在作用。相对于野生型成纤维细胞， Jnk1 ？/？细胞中的TBP降低，而 Jnk2 ？/？单元格。同样，人肝癌细胞中JNK1的减少会降低TBP表达，而JNK2的减少会增强TBP表达。 JNK介导的TBP表达调节通过其靶向Elk-1的能力在转录水平发生，Elk-1可以直接调节TBP启动子以响应表皮生长因子刺激。 JNK1增加，而JNK2减少，这是Elk-1的磷酸化状态，该状态在TBP启动子内的特定位点差异影响Elk-1的占用。这些JNK介导的TBP表达改变仅用于调节c-Jun表达和成纤维细胞增殖速率。这些研究发现了几个新的分子事件，这些事件区分了JNK1和JNK2的功能，这些功能对其调节细胞增殖至关重要。

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