2012 Fiscal Year Final Research Report
SCF^<Fbxl12>modulates the abundance of p21 in concert with proteasome activator PA28γ
| Project/Area Number |
23770218
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cell biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | 細胞周期 / タンパク質分解 |
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| Research Abstract |
The ubiquitin-proteasome system (UPS) plays an important role for the regulation of cell cycle and DNA damage response. The SCF complexes are the major ubiquitin ligases that control these processes. In this study, we found that SCF^<Fbxl12>associates with proteasomal subunit PA28γ and cyclin-dependent kinase (CDK) inhibitor p21, and is involved in the regulation of p21 abundance in cell. In addition, this complex-forming ability is attenuated by UV stimulation. We also found that the intronic regions of Fbxl12 acts as an alternative promoter and induces expression of short form of Fbxl12 in response to UV irradiation. Taken together, these data demonstrate that Fbxl12 is a key mediator that links UV irradiation to p21 degradation, and this novel function of Fbxl12 may provide an insight into the mechanisms by which DNA damage mediates p21 stabilization.
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