Inhibition of G1 to S Phase Progression by a Novel Zinc Finger Protein P58TFL at P-bodies
Inhibition of G1 to S Phase Progression by a Novel Zinc Finger Protein P58TFL at P-bodies
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DOI：
10.1158/1541-7786.mcr-08-0511
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发表时间：
2009-06-01
影响因子：
5.2
通讯作者：
Matsui, Toshimitsu
中科院分区：
文献类型：
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作者：
Minagawa, Kentaro;Katayama, Yoshio;Matsui, Toshimitsu
我们最近报道了转化滤泡性淋巴瘤中免疫球蛋白 (Ig) 轻链 kappa 位点基因与可能的抑癌基因 TFL 的易位。然而，细胞转化中的功能意义仍有待阐明。在这里，我们首先鉴定了通过选择性剪接衍生的两种基因产物：P58(TFL)和P36(TFL)。该表达在正常人淋巴细胞中显着，但在某些白血病/淋巴瘤细胞系中存在缺陷。在小鼠 pro-B 细胞系 Ba/F3 和人白血病细胞系 Jurkat 中过度表达任一蛋白，可通过抑制视网膜母细胞瘤蛋白 (Rb) 磷酸化来抑制 G(1) 至 S 期进展。显性基因产物 P58(TFL) 与 mRNA 加工体标记、真核翻译起始因子 2C 和 DCP1 脱帽酶同源物 A 共定位，但不与应激颗粒标记 T 细胞胞内抗原 1 共定位于细胞质中。结合独特的 CCCH 型锌指基序，本研究表明 P58(TFL) 可以通过细胞周期调节因子的转录后修饰（至少部分位于 Rb 的上游）在细胞生长调节中发挥重要作用。 (摩尔癌症研究 2009;7(6):880-9)
We recently reported the translocation of the immunoglobulin (Ig) light chain kappa locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58(TFL) and P36(TFL), derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G(1) to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58(TFL), colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58(TFL) could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb. (Mol Cancer Res 2009;7(6):880-9)