共查询到20条相似文献,搜索用时 15 毫秒
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Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function 总被引:22,自引:0,他引:22
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HIF-1 and p53: communication of transcription factors under hypoxia 总被引:14,自引:0,他引:14
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Hypoxia inhibits G1/S transition through regulation of p27 expression 总被引:26,自引:0,他引:26
Gardner LB Li Q Park MS Flanagan WM Semenza GL Dang CV 《The Journal of biological chemistry》2001,276(11):7919-7926
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Cho YS Bae JM Chun YS Chung JH Jeon YK Kim IS Kim MS Park JW 《Biochimica et biophysica acta》2008,1783(2):323-333
The cyclin-dependent kinase inhibitor p21(WAF1/Cip1) plays a central role in a spatial and temporal balance of epidermal keratinocyte proliferation and growth arrest. However, what controls p21 expression in keratinocytes remains uncertain. Hypoxia-inducible factor 1alpha (HIF-1alpha) does not only express a variety of genes essential for hypoxic adaptation, but also up-regulates p21 so as to slow down cell cycle under hypoxic conditions. In the present study, we examined the role of HIF-1alpha in p21-mediated growth arrest of keratinocyte. Keratinocyte proliferation was arrested in the G1 phase at a high cell density. p21 was also up-regulated in a cell density-dependent manner and was found to be highly expressed in epidermal keratinocytes of normal human skins. In addition, in the same specimens and cells, we noted robust HIF-1alpha expression. HIF-1alpha siRNAs inhibited p21 expression and released the G1 arrest. In vivo, moreover, the intradermal injection of HIF-1alpha siRNA attenuated p21 expression in rat epidermis and induced skin hyperplasia. Mechanistically, we propose that the production of mitochondrial reactive oxygen species and the activation of the MEK/ERK pathway are involved in the HIF-1alpha stabilization in keratinocytes. These results imply that HIF-1alpha functions as an up-stream player in the p21-mediated growth arrest of keratinocytes. 相似文献
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Binding of natively unfolded HIF-1alpha ODD domain to p53 总被引:1,自引:0,他引:1