共查询到20条相似文献,搜索用时 15 毫秒
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Beischlag TV Taylor RT Rose DW Yoon D Chen Y Lee WH Rosenfeld MG Hankinson O 《The Journal of biological chemistry》2004,279(52):54620-54628
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Rivera SP Wang F Saarikoski ST Taylor RT Chapman B Zhang R Hankinson O 《The Journal of biological chemistry》2007,282(15):10881-10893
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Identification of alternative spliced variants of human hypoxia-inducible factor-1alpha 总被引:12,自引:0,他引:12
Gothié E Richard DE Berra E Pagès G Pouysségur J 《The Journal of biological chemistry》2000,275(10):6922-6927
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D?rthe M Katschinski Lu Le Susann G Schindler Tim Thomas Anne K Voss Roland H Wenger 《Cellular physiology and biochemistry》2004,14(4-6):351-360
Hypoxia-inducible factor (HIF) alpha subunits are induced under hypoxic conditions, when limited oxygen supply prevents prolyl hydroxylation-dependent binding of the ubiquitin ligase pVHL and subsequent proteasomal degradation. A short normoxic half-life of HIF-alpha and a very rapid hypoxic protein stabilization are crucial to the cellular adaptation to changing oxygen supply. However, the molecular requirements for the unusually rapid mechanisms of protein synthesis, folding and nuclear translocation are not well understood. We and others previously found that the chaperone heat-shock protein 90 (HSP90) can interact with HIF-1alpha in vitro. Here we show that HSP90 also interacts with HIF-2alpha and HIF-3alpha, suggesting a general involvement of HSP90 in HIF-alpha stabilization. The PAS B domain, common to all three alpha subunits, was required for HSP90 interaction. ARNT competed with HSP90 for binding to the PAS B domain since an excess of either component inhibited the activity of the other. HSP90 as well as the heterocomplex members HSP70 and p23, but not HSP40, were detected in immunoprecipitations of endogenous cellular HIF-1alpha. While HSP90 and HSP70 bound to HIF-1alpha predominantly under normoxic conditions, ARNT bound to HIF-1alpha primarily under hypoxic conditions, suggesting that ARNT displaced HSP90 from HIF-1alpha following nuclear translocation. Hypoxic accumulation of HIF-1alpha was delayed in a novel cell model deficient for HSP90beta as well as after treatment of wild-type cells with the HSP90 inhibitor geldanamycin, suggesting that HSP90 activity is involved in the rapid HIF-1alpha protein induction. 相似文献