2007 Fiscal Year Final Research Report Summary
Nuclear function of protein kinase CK2 on cell cycle regulation
| Project/Area Number |
18570133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
KATO Miwako Fukushima Medical University, SCHOOL OF MEDICINE, DEPARTMENT OF BIOMOLECULAR SCIENCE, LECTURER (40192538)
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| Project Period (FY) |
2006 – 2007
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| Keywords | CK2 / Cell cycle / nucleus / hnRNP / 細胞核 |
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| Research Abstract |
Casein kinase 2 (CK2) is a highly conserved and ubiquitous eukaryotic Ser/Thr protein kinase. Genetic, biochemical and cell biological studies have indicated the involvement of this enzyme in the control of cell proliferation and in signal transduction. The regulation of CK2 is not well defined, and it has been considered a constitutively non-regulated protein kinase. We show that CK2 activation occurred during the progression of cell cycle in response to FBS stimuli of Go arrested cells. Importantly, we show that as the downstream target for CK2, the phosphorylation of eukaryotic translation-initiation factor eIF5 by CK2 may play a critical role in cell-cycle progression. Expression of eIF5 mutants that lack those phosphorylation sites by CK2 reveals that these mutants have a dominant-negative effect on phosphorylation of endogenous eIF5, as well as a significant reduction in the formation of the mature complex, the growth rate, and the expression of cell cycle-regulated proteins. Also, a pool of CK2 translocates into the nuclear fraction following its activation during the progression of the cell cycle. We identified molecules associated with CK2 in the nuclear fraction, by mass spectrometric analysis and by antibody micro arrays. Consistent with these findings, we report that CK2 may be involved in the regulation of cell cycle progression through the phosphorylation of a key molecule for translation initiation and of nuclear substrates upon activation of CK2 by itself.
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