2005 Fiscal Year Final Research Report Summary
In vivo analysis of mechanisms underlying cellular differentiation and proliferation control
| Project/Area Number |
14033217
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Fukui (2004-2005)
福井医科大学 (2002-2003) |
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Principal Investigator |
YOKOTA Yoshmurn University of Fukui, School of Medical Sciences, Professor, 医学部, 教授 (50222386)
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| Co-Investigator(Kenkyū-buntansha) |
KUROOKA Hisanori University of Fukui, School of Medical Sciences, Associate Professor, 医学部, 助教授 (00293879)
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| Project Period (FY) |
2002 – 2005
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| Keywords | Gene / Cancer / Gene expression / Cellular differentiatiom / Proliferation / Network / Transcriptional regulator |
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| Research Abstract |
d2, a negative regulator of basic helix-loop-helix transcription factors, plays an important role in the regulation of cellular differentiation and proiferation. The aim of this research project is to reveal the functions of Id2 in the network of physiological responses and to elucidate molecular mechanisms underlying the regulation of cellular differentiation and proliferation, by analyzing Id2 KO nice and biochemical activities of Id2 in vitro. We obtained the following findings :
1. Functions of Id2 in the proliferation of mammary epithelial cells
Id2 KO nice exhibit severely disturbed proliferation of mammary epithelial cells during pregnancy, similar to C/EBP KO nice. We demonstrated that Id2 is a direct target of C/EBP^in pregnant mammary epithelial cells. On the other hand, crossing experiments of Id2 KO nice with MMTV-cyclin D1 fransgenic nice demonstrated that Id2-deficiency reduces the incidence of mammary hyperplasia and tumorigenesis in the transgenic nice, while overexpression of cyclin D1 does not rescue the lactation defect of 1d2 KO nice.
2. Molecular basis of intracellular localization of Id proteins
We demonstrated that the HLH and C-terminal regions of Id2 contain the nuclear localization and CRM1-dependent nuclear export signals, respectively. In addition, the nuclear export signal of Id1 was found to be located in the C-terminal side of the HLH region.
3. A role for 1d2 in proliferation control of neural stem/precursor cells
Id2 KO mice display size-reduction of the olfactory bulb after postnatal day 8. We demonstrated that this is due to elevated expression of p21, a CDK inhibitor, in neural stem/precursor cells in the subventricular zone of 1d2 KO mice.
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