Mitogenic stimulation of resting T cells causes rapid phosphorylation of the transcription factor LSF and increased DNA-binding activity.
Mitogenic stimulation of resting T cells causes rapid phosphorylation of the transcription factor LSF and increased DNA-binding activity.
复制标题
静息 T 细胞的有丝分裂刺激导致转录因子 LSF 快速磷酸化并增加 DNA 结合活性。
DOI：
10.1101/gad.11.11.1435
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发表时间：
1997
影响因子：
10.5
通讯作者：
Hansen,U
中科院分区：
文献类型：
--
作者：
Volker,JL;Rameh,LE;Zhu,Q;DeCaprio,J;Hansen,U
哺乳动物转录因子LSF（CP 2/LBP-1c）结合由细胞生长信号调节的细胞启动子。我们在这里证明，LSF-DNA结合活性是显着调节诱导人外周血T淋巴细胞的细胞生长。在这些细胞的促有丝分裂刺激的15分钟内，LSF-DNA结合活性的水平增加了5倍。LSF蛋白在细胞核中的水平在此期间保持恒定。然而，在电泳迁移率的LSF，归因于磷酸化的快速下降，与DNA结合活性的增加。pp 44（ERK 1）在体内磷酸化的相同残基上体外磷酸化LSF，特别是在氨基酸位置291处，如突变体分析所示。作为磷酸化和DNA结合活性之间的因果关系的直接验证，在体外用磷酸酶处理LSF既增加了蛋白质的电泳迁移率，又降低了LSF-DNA结合活性。随着T细胞从静止状态进展到复制状态，LSF-DNA结合活性的这种调节揭示了LSF活性在细胞生长期间受到调节，并表明LSF调节生长响应性启动子。
The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.