The RNA-Binding Protein RBM3 Is Required for Cell Proliferation and Protects Against Serum Deprivation-Induced Cell Death
The RNA-Binding Protein RBM3 Is Required for Cell Proliferation and Protects Against Serum Deprivation-Induced Cell Death
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DOI：
10.1203/pdr.0b013e3181c13326
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Buehrer, Christoph
中科院分区：
文献类型：
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作者：
Wellmann, Sven;Truss, Matthias;Buehrer, Christoph
快速生长的细胞通常会遇到缺氧和其他不利条件。rna结合蛋白RBM3 （rna结合基序蛋白3）是在低温和缺氧条件下转录诱导的，最近通过环氧化酶-2 （COX-2）信号传导机制与结肠癌细胞的存活有关。免疫组织化学我们发现RBM3在多种恶性和增殖组织中表达强烈，但在静止和终末分化细胞中表达低。通过实时RT-PCR和免疫印迹检测，在血清剥夺或接触抑制的成纤维细胞和人胚胎肾（HEK293）细胞中RBM3的表达与增殖率密切相关。sirna介导的RBM3敲低降低了细胞活力，最终导致细胞死亡，这与caspase-3介导的细胞凋亡、细胞周期阻滞或COX-2调节无关。相反，RBM3过表达使细胞免于血清饥饿的死亡。通过（14）C丝氨酸和(3)H苯丙氨酸掺入测量，这与翻译率的增加有关。总之，RBM3是在不利的微环境中提供细胞生存优势的关键因素，可能是通过恢复翻译功效。（儿科研究67:35-41,2010）
Hypoxia and other adverse conditions are commonly encountered by rapidly growing cells. The RNA-binding protein RBM3 (RNA-binding motif protein 3), which is transcriptionally induced by low temperature and hypoxia, has recently been implicated in survival of colon cancer cells by mechanisms involving cyclooxygenase-2 (COX-2) signaling. Immunohistochemically we found strong RBM3 expression in a variety of malignant and proliferating tissues but low expression in resting and terminally differentiated cells. RBM3 expression in fibroblasts and human embryonal kidney (HEK293) cells subjected to serum deprivation or contact inhibition closely paralleled proliferation rates, assessed by real-time RT-PCR and immunoblotting. siRNA-mediated RBM3 knockdown reduced cell viability and finally led to cell death, which did not involve caspase-3-mediated apoptosis, cell cycle arrest, or COX-2 regulation. In contrast, RBM3 over-expression rescued cells from death under serum starvation. This was associated with increased translation rates, as measured by (14)C serine and (3)H phenylalanine incorporation. Together, RBM3 is a critical factor providing cellular survival advantages in an adverse microenvironment presumably by restoring translation efficacy. (Pediatr Res 67: 35-41, 2010)