Ribosomal protein S6 is highly expressed in non-Hodgkin lymphoma and associates with mRNA containing a 5' terminal oligopyrimidine tract.
Ribosomal protein S6 is highly expressed in non-Hodgkin lymphoma and associates with mRNA containing a 5' terminal oligopyrimidine tract.
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DOI：
10.1038/onc.2010.533
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发表时间：
2011-03-31
期刊：
影响因子：
8
通讯作者：
Gartenhaus, R. B.
中科院分区：
文献类型：
--
作者：
Hagner, P. R.;Mazan-Mamczarz, K.;Dai, B.;Balzer, E. M.;Corl, S.;Martin, S. S.;Zhao, X. F.;Gartenhaus, R. B.
细胞核中肿瘤发生和形态学改变的分子机制正逐渐成为人们关注的焦点。核仁是核糖体亚单位形成的细胞器。核糖体生物发生通过核糖体RNA（rRNA）的转录、rRNA加工和核糖体蛋白的产生而发生。这些过程中的任何一个错误都可能导致细胞翻译失调，这在多种癌症和“核糖体病”中很明显。蛋白质合成失调可能是通过核糖体蛋白的过表达实现的，如在具有升高水平的核糖体蛋白S11和S14的原发性白血病母细胞中所见。在这项研究中，我们证明了核糖体蛋白S6（RPS6）在原发性弥漫性大B细胞淋巴瘤（DLBCL）样本中高度表达。与对照shRNA相比，用特异性靶向短发夹RNA（shRNA）慢病毒对RPS6蛋白水平进行遗传调节导致活跃增殖的细胞群体减少。低剂量雷帕霉素处理已被证明会影响5′端寡嘧啶（5′ TOP）道mRNA的翻译，该mRNA编码翻译机制，暗示RPS6参与5′ TOP翻译。最近，研究表明，通过特异性小抑制RNA敲低RPS6破坏40S核糖体生物合成，将RPS6定义为5′ TOP翻译的关键调节因子。我们首次发现RPS6与含有5′ TOP区的多个mRNA相关。这些发现扩展了我们对DLBCL中核糖体生物发生和蛋白质合成失调的机制的理解。
The molecular mechanism(s) linking tumorigenesis and morphological alterations in the nucleolus are presently coming into focus. The nucleolus is the cellular organelle in which the formation of ribosomal subunits occurs. Ribosomal biogenesis occurs through the transcription of ribosomal RNA (rRNA), rRNA processing and production of ribosomal proteins. An error in any of these processes may lead to deregulated cellular translation, evident in multiple cancers and ‘ribosomopathies’. Deregulated protein synthesis may be achieved through the overexpression of ribosomal proteins as seen in primary leukemic blasts with elevated levels of ribosomal proteins S11 and S14. In this study, we demonstrate that ribosomal protein S6 (RPS6) is highly expressed in primary diffuse large B-cell lymphoma (DLBCL) samples. Genetic modulation of RPS6 protein levels with specifically targeted short hairpin RNA (shRNA) lentiviruses led to a decrease in the actively proliferating population of cells compared with control shRNA. Low-dose rapamycin treatments have been shown to affect the translation of 5′ terminal oligopyrimidine (5′ TOP) tract mRNA, which encodes the translational machinery, implicating RPS6 in 5′ TOP translation. Recently, it was shown that disruption of 40S ribosomal biogenesis through specific small inhibitory RNA knockdown of RPS6 defined RPS6 as a critical regulator of 5′ TOP translation. For the first time, we show that RPS6 associates with multiple mRNAs containing a 5′ TOP tract. These findings expand our understanding of the mechanism(s) involved in ribosomal biogenesis and deregulated protein synthesis in DLBCL.
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影响因子：
8
作者：
Lee-Fruman, KK;Kuo, CJ;Blenis, J
通讯作者：
Blenis, J
影响因子：
8
作者：
Mazan-Mamczarz, K.;Hagner, P. R.;Corl, S.;Srikantan, S.;Wood, W. H.;Becker, K. G.;Gorospe, M.;Keene, J. D.;Levenson, A. S.;Gartenhaus, R. B.
通讯作者：
Gartenhaus, R. B.
影响因子：
5.3
作者：
Galbán, S;Martindale, JL;Gorospe, M
通讯作者：
Gorospe, M
影响因子：
6.5
作者：
Ganapathi, Karthik A.;Shimamura, Akiko
通讯作者：
Shimamura, Akiko
DOI：
10.1016/0167-4781(95)00224-3
发表时间：
1996-03-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Law, PTW;Tsui, SKW;Waye, MMY
通讯作者：
Waye, MMY