2002 Fiscal Year Final Research Report Summary
Anakysis of GATA-3 function in proliferation and differentiation of kerationocytes
| Project/Area Number |
13670865
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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 |
Dermatology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KAWACHI Yasuhiro Inst. of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (00272196)
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| Project Period (FY) |
2001 – 2002
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| Keywords | GATA-3 / Keratinocytes |
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| Research Abstract |
In epidermal keratinocytes, we demonstrated that GATA-3 was more abundant in differentiated keratinocytes than undifferentiated keratinocytes, suggesting that GATA-3 might contribute to differntiatioirspecific gene regulation. We previously showed that c-Fos and Sp1 activate the loricrin promoter activity in differentiated keratinocytes while c-Jun and Sp3 suppress it in undifferentiated keratinocytes. Thus, we tested the cooperative tarnsactivation of loricrin promoter activity by GATA-3, c-Fos and Sp1. Transactivation experiments presented here provide evidence that GATA-3, c-Fos and Sp1 can activate the loricrin promoter transcription in a synergistic manner even though the GATA-3 binding motif is deleted from the promoter. These results strongly suggest the interaction among those proteins. Thus, we examined the physical binding among GATA-3, AP-1 and Sp1/Sp3. In vitro binding by means of a glutathione S-transferase pull down assay showed that c-Jun/c-Fos could directly associate with GATA-3. However, binding affinity of GATA-3 with Sp1 was much less than that with c-Fos, These results suggest that GATA-3 can interact with c-Fos directly while GATA-3 may interact with Sp1 via other transcription factors or cofactors.
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[Publications] Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, Bickenbach J, Kawachi Y, Suga Y, Zhou Z, Huber M, Hohl D, Kartasova T, Jarnik M, Steven AC, Roop DR.: "Lessons from loricrin-deficient mice : compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein"Journal of Cell Biology. 151. 389-400 (2000)
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