Regulation of gene expression of proteasomes (multi-protease complexes) during growth and differentiation of human hematopoietic cells.
Regulation of gene expression of proteasomes (multi-protease complexes) during growth and differentiation of human hematopoietic cells.
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DOI：
10.1016/s0021-9258(19)37158-3
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发表时间：
1992-09
期刊：
影响因子：
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通讯作者：
N. Shimbara;E. Orino;S. Sone;T. Ogura;M. Takashina;M. Shono;T. Tamura;H. Yasuda;K. Tanaka;A. Ichihara
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文献类型：
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作者：
N. Shimbara;E. Orino;S. Sone;T. Ogura;M. Takashina;M. Shono;T. Tamura;H. Yasuda;K. Tanaka;A. Ichihara
我们报道了蛋白酶体在各种造血肿瘤细胞中以异常高的水平表达（Kumatori, A.、Tanaka, K.、Inamura, N.、Sone, S.、Ogura, T.、Matsumoto, T.、Tachikawa, T.、Shin, S.和 Ichihara, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87， 7071-7075）。在本研究中，我们检测了健康成人外周 T 淋巴细胞生长和人白血病细胞系分化过程中蛋白酶体表达的变化。在植物血凝素和白细胞介素 2 等有丝分裂原诱导的静息 T 细胞增殖过程中，观察到编码多个蛋白酶体亚基的 mRNA 上调。相反，各种未成熟白血病细胞系（例如HL-60早幼粒细胞白血病细胞和K562红白血病细胞）在体外终末分化为单核细胞、粒细胞和红系细胞，通过各种诱导剂引起蛋白酶体表达快速且显着的下调，与细胞类型、分化方向或信号类型无关。通过[35S]甲硫氨酸掺入测量，21-31 kDa 的蛋白酶体亚基及其 35-110 kDa 的相关成分的合成，在有丝分裂原激活的 T 细胞和未刺激的 HL-60 细胞（生长迅速）中比在静息和分化细胞中要高得多，表明蛋白酶体的 mRNA 水平与其翻译活性存在明显的相关性。然而，在免疫化学上，在增殖和分化的诱导和未诱导状态下，没有发现这些细胞中蛋白酶体的细胞含量存在可检测到的差异，这表明快速增殖的细胞中蛋白酶体的周转加速。最大蛋白酶体亚基 C2 的反义寡脱氧核苷酸对蛋白酶体表达的抑制导致 T 淋巴细胞的细胞周期进程部分停滞，表明蛋白酶体的上调对于细胞增殖是必不可少的。我们还观察到增殖T细胞中蛋白酶体的核分数增加，并且在HL-60细胞分化过程中蛋白酶体在细胞核和细胞质之间快速移动。
We have reported that proteasomes are expressed at abnormally high levels in various hematopoietic tumor cells (Kumatori, A., Tanaka, K., Inamura, N., Sone, S., Ogura, T., Matsumoto, T., Tachikawa, T., Shin, S., and Ichihara, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7071-7075). In the present study, we examined changes in the expressions of proteasomes during growth of peripheral T-lymphocytes from healthy adults and differentiation of human leukemic cell lines. Up-regulation of mRNAs encoding multiple proteasome subunits was observed during proliferation of resting T-cells induced by mitogens such as phytohemagglutinin and interleukin-2. In contrast, in vitro terminal differentiation into monocytic, granulocytic, and erythroid cells of various immature leukemic cell lines, such as HL-60 promyelocytic leukemia cells and K562 erythroleukemia cells, by various inducing agents caused rapid and marked down-regulation of proteasomes expression, independently of the cell type, direction of differentiation, or type of signal. The syntheses of proteasome subunits of 21-31 kDa and their associated components of 35-110 kDa, measured by [35S]methionine incorporation, were much higher in mitogen-activated T-cells and unstimulated HL-60 cells, which grow rapidly, than in resting and differentiated cells, indicating apparent correlations of the mRNA levels of proteasomes with their translational activities. However, immunochemically, no detectable difference in the cellular contents of proteasomes was found in these cells in induced and uninduced states for proliferation and differentiation, suggesting accelerated turnover of proteasomes in rapidly proliferating cells. Inhibition of proteasome expression by an antisense oligodeoxynucleotide for the largest proteasome subunit, C2, caused partial arrest of cell cycle progression of T-lymphocytes, suggesting that up-regulation of proteasomes is indispensable for proliferation of the cells. We also observed that the nuclear fraction of proteasomes increased in proliferating T-cells and that proteasomes moved rapidly between the nucleus and cytoplasm during differentiation of HL-60 cells.