1999
DOI: 10.1038/20459
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Abstract: Hypoxia-inducible factor-1 (HIF-1) has a key role in cellular responses to hypoxia, including the regulation of genes involved in energy metabolism, angiogenesis and apoptosis. The alpha subunits of HIF are rapidly degraded by the proteasome under normal conditions, but are stabilized by hypoxia. Cobaltous ions or iron chelators mimic hypoxia, indicating that the stimuli may interact through effects on a ferroprotein oxygen sensor. Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour supp… Show more

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Cited by 4,469 publications
(3,370 citation statements)
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References 29 publications
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“…We and others have recently shown that GRIM-19 binds to STAT3 and inhibits its gene stimulating functions (Lufei et al, 2003;Zhang et al, 2003). In this regard, GRIM-19 appears to behave like the VHL protein, which binds to transcription factor HIF1 and prevents its gene stimulatory function (Iliopoulos et al, 1996;Maxwell et al, 1999). Among the members of the STAT family, GRIM-19 preferentially associates with STAT3 .…”
Section: Discussionmentioning
confidence: 97%
“…We and others have recently shown that GRIM-19 binds to STAT3 and inhibits its gene stimulating functions (Lufei et al, 2003;Zhang et al, 2003). In this regard, GRIM-19 appears to behave like the VHL protein, which binds to transcription factor HIF1 and prevents its gene stimulatory function (Iliopoulos et al, 1996;Maxwell et al, 1999). Among the members of the STAT family, GRIM-19 preferentially associates with STAT3 .…”
Section: Discussionmentioning
confidence: 97%
“…The response of metastatic RCC to conventional chemotherapy is poor, but characterisation of the molecular pathology of RCC can provide a basis for developing novel therapeutic approaches. This is exemplified by the VHL TSG paradigm in which (a) inactivation of VHL is the most common event in sporadic clear cell RCC (Latif et al, 1993;Foster et al, 1994;Herman et al, 1994;Clifford et al, 1998); (b) VHL inactivation leads to stabilisation of HIF-1 and HIF-2 transcription factors and activation of hypoxic response genes that drive renal tumourigenesis (Maxwell et al, 1999); and (c) inhibitors (for example, tyrosine kinase inhibitors such as sorafenib and sunitinib) of HIF target pathways are active in the treatment of metastatic RCC (Chowdhury et al, 2008). Hence, identification of frequently inactivated RCC TSGs can provide a basis for novel therapeutic interventions.…”
Section: Ct Bstu1mentioning
confidence: 99%
“…Expression of BNIP3, which is dramatically increased in response to hypoxia, is regulated in part by hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor comprised of an oxygenregulated a subunit (HIF-1a) and a stale nuclear factor (HIF-1b/ ARNT), and known to be a mediator of the hypoxic response (Semenza, 1999). Under normoxic conditions, HIF-1a is rapidly degraded by proteasome after being targeted for ubiquitination (Maxwell et al, 1999). Under hypoxic conditions, degradation of HIF-1a is suppressed, and expression of BNIP3 is induced.…”
mentioning
confidence: 99%