Cytoskeleton-interacting LIM-domain protein CRP1 suppresses cell proliferation and protects from stress-induced cell death
Cytoskeleton-interacting LIM-domain protein CRP1 suppresses cell proliferation and protects from stress-induced cell death
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DOI：
10.1016/j.yexcr.2007.11.024
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发表时间：
2008-02-15
影响因子：
3.7
通讯作者：
Laiho, Marikki
中科院分区：
文献类型：
--
作者：
Latonen, Leena;Jarvinen, Paivi M.;Laiho, Marikki
富含半胱氨酸蛋白 (CRP) 家族的成员是与肌动蛋白细胞骨架相互作用的 LIM 结构域蛋白，已知在肌肉细胞分化中发挥作用。我们之前发现，CRP1（该家族的创始成员）在人类二倍体成纤维细胞中由紫外线辐射诱导转录[M. Gentile，L. Latonen，M. Laiho，紫外线辐射诱导的 DNA 损伤引起的细胞周期停滞和细胞凋亡是转录上高度分歧的反应，核酸研究。 31（2003）4779-4790]。在这里，我们表明 CRP1 是由生长抑制信号诱导的，例如细胞密度增加，以及紫外线辐射或十字孢菌素诱导的细胞毒性应激。我们发现高水平的 CRP1 与肌成纤维细胞谱系的分化相关形态相关，并且异位 CRP1 的表达抑制细胞增殖。在紫外线和十字孢菌素诱导的应激后，CRP1 的表达提供了生存优势，这通过减少细胞死亡和增加细胞代谢活动和附着来证明。我们的研究发现CRP1是一种新型应激反应因子，并为其生长抑制和细胞保护功能提供了证据。 (C) 2007 Elsevier Inc. 保留所有权利。
Members of the cysteine-rich protein (CRP) family are actin cytoskeleton-interacting LIM-domain proteins known to act in muscle cell differentiation. We have earlier found that CRP1, a founding member of this family, is transcriptionally induced by UV radiation in human diploid fibroblasts [M. Gentile, L. Latonen, M. Laiho, Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses, Nucleic Acids Res. 31 (2003) 4779-4790]. Here we show that CRP1 is induced by growth-inhibitory signals, such as increased cellular density, and cytotoxic stress induced by UV radiation or staurosporine. We found that high levels of CRP1 correlate with differentiation-associated morphology towards the myofibroblast lineage and that expression of ectopic CRP1 suppresses cell proliferation. Following UV- and staurosporine-induced stresses, expression of CRP1 provides a survival advantage evidenced by decreased cellular death and increased cellular metabolic activity and attachment. our studies identify that CRP1 is a novel stress response factor, and provide evidence for its growth-inhibitory and cytoprotective functions. (C) 2007 Elsevier Inc. All rights reserved.