2011 Fiscal Year Final Research Report
A molecular scaffold HIC-5-and KLF4-dependent mechanism transactivates p21^<Cip1> in response to loss of anchorage
| Project/Area Number |
22790327
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 足場依存性増殖 / 非依存性増殖 |
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| Research Abstract |
In this study, we show that HIC-5 is also engaged in transcriptional upregulation of a cyclin-dependent kinase inhibitor(CKI) p21^<Cip1> in non-adherent cells, thereby contributing to the growth arrest. The transactivation of p21^<Cip1> was regulated at the upstream element, designate detachment-responsive element(DRE), consisting of binding sites for the two transcription factors, Kruppel-like KLF4 and runt-related RUNX1 ; Both sites were necessary but not sufficient alone for the transactivation. HIC-5 was critically involved in the transactivation by facilitating the tethering process of KLF4 onto the DNA sites in association with its increased localization to the nuclear matrix under non-adherent conditions. At the Runx1 site, a LIM-only protein, CRP2, imposed negative regulation under adherent conditions, which was assumingly removed upon loss of anchorage and contributed to the elevated transcriptional activity of DRE collaboratively with the regulation at the KLF4 sites. In conclusion, this study uncovered a novel transcriptional mechanism regulating gene expression in a detachment-dependent manner.
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