Deregulation of Translational Control of the 65-kDa Regulatory Subunit (PR65α) of Protein Phosphatase 2A Leads to Multinucleated Cells (*)

Deregulation of Translational Control of the 65-kDa Regulatory Subunit (PR65α) of Protein Phosphatase 2A Leads to Multinucleated Cells (*)
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蛋白磷酸酶 2A 65-kDa 调节亚基 (PR65α) 翻译控制的失调导致多核细胞 (*)

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发表时间:
1995
影响因子:
4.8
通讯作者:
B. Hemmings
B. Hemmings
中科院分区:
生物学2区
文献类型:
--
作者:
S. Wera;Anne Fernandez;N. Lamb;P. Turowski;M. Hemmings;R. E. Mayer;B. Hemmings

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编码蛋白磷酸酶2A(PP 2A)的65-kDa调节亚基(PR 65 α)的mRNA的有效翻译被5′-非翻译区(5′-UTR)中的框外上游AUG和稳定的茎环结构(ΔG = −55.9 kcal/mol)阻止。5′-UTR的缺失允许PR 65 α信息在体外的有效翻译和在COS-1细胞中的过表达。将5′-UTR插入到β-半乳糖苷酶前导序列中在体外和体内显著抑制β-半乳糖苷酶信息的翻译,证实该序列作为有效的翻译调控序列起作用。用缺少5′-UTR的PR 65 α表达载体转染或显微注射的细胞表达高水平的PR 65 α,在细胞核和细胞质中积累。PR 65 α过表达的大鼠胚胎成纤维细胞(REF-52细胞)变为多核。这些数据和以前的结果(迈耶-Jaekel,R。E、Ohkura,H.,戈梅斯河松克尔角E、Baumgartner,S.,亨明斯,B。一、和格洛弗,D. M.(1993)Cell 72,621-633)表明PP 2A参与有丝分裂和胞质分裂的调节。
Efficient translation of the mRNA encoding the 65-kDa regulatory subunit (PR65α) of protein phosphatase 2A (PP2A) is prevented by an out of frame upstream AUG and a stable stem-loop structure (ΔG = −55.9 kcal/mol) in the 5′-untranslated region (5′-UTR). Deletion of the 5′-UTR allows efficient translation of the PR65α message in vitro and overexpression in COS-1 cells. Insertion of the 5′-UTR into the β-galactosidase leader sequence dramatically inhibits translation of the β-galactosidase message in vitro and in vivo, confirming that this sequence functions as a potent translation regulatory sequence. Cells transfected or microinjected with a PR65α expression vector lacking the 5′-UTR, express high levels of PR65α, accumulating in both nucleus and cytoplasm. PR65α overexpressing rat embryo fibroblasts (REF-52 cells) become multinucleated. These data and previous results (Mayer-Jaekel, R. E., Ohkura, H., Gomes, R., Sunkel, C. E., Baumgartner, S., Hemmings, B. A., and Glover, D. M.(1993) Cell 72, 621-633) suggest that PP2A participates in the regulation of both mitosis and cytokinesis.
DOI: 10.1073/pnas.83.24.9373
发表时间: 1986-12-01
影响因子: 11.1
作者:
FREIER, SM;KIERZEK, R;TURNER, DH
通讯作者: TURNER, DH
DOI: 10.1073/pnas.84.14.4880
发表时间: 1987-07-01
影响因子: 11.1
作者:
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通讯作者: MUMBY, MC
DOI: 10.1021/bi00205a023
发表时间: 1994-10
期刊: Biochemistry
影响因子: 2.9
作者:
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DOI: 10.1126/science.7939721
发表时间: 1994-10-28
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: LAWRENCE, JC
DOI: 10.1128/mcb.7.10.3438
发表时间: 1987-10-01
影响因子: 5.3
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