Putative Control of Angiogenesis in Hemangioblastomas by the von Hippel-Lindau Tumor Suppressor Gene

Stratmann, Rembert; Krieg, Marion; Haas, Richard de Goeij-de; Plate, Karl H.

doi:10.1097/00005072-199711000-00009

Cited by 68 publications

(28 citation statements)

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“…Second, kinetics of its hypoxia response mostly resembles the one of HIF-1a-independent gene GADD153 and differs from HIF1a-dependent genes p21-Waf1 and VEGF (Carmeliet et al, 1998;Liu et al, 1995). Third, our preliminary results demonstrate that in the VHL-deficient 786-0 renal carcinoma cell line with constitutively activated HIF-1a (Stratmann et al, 1997), expression of Hi95 is low and is dramatically stimulated following 24 h of DFO treatment (A Budanov and PM Chumakov, unpublished observation), contrasting the constitutive expression of HIF-1a-dependent genes.…”

Section: Discussionmentioning

confidence: 65%

Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

et al. 2002

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cDNA microarray hybridization was used in an attempt to identify novel genes participating in cellular responses to prolonged hypoxia. One of the identified novel genes, designated Hi95 shared significant homology to a p53-regulated GADD family member PA26. In addition to its induction in response to prolonged hypoxia, the increased Hi95 transcription was observed following DNA damage or oxidative stress, but not following hyperthermia or serum starvation. Whereas induction of Hi95 by prolonged hypoxia or by oxidative stress is most likely p53-independent, its induction in response to DNA damaging treatments (g-or UV-irradiation, or doxorubicin) occurs in a p53-dependent manner. Overexpression of Hi95 fulllength cDNA was found toxic for many types of cultured cells directly leading either to their apoptotic death or to sensitization to serum starvation and DNA damaging treatments. Unexpectedly, conditional overexpression of the Hi95 cDNA in MCF7-tet-off cells resulted in their protection against cell death induced by hypoxia/glucose deprivation or H 2 O 2 . Thus, Hi95 gene seems to be involved in complex regulation of cell viability in response to different stress conditions.

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Section: Discussionmentioning

confidence: 65%

Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

et al. 2002

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“…786-0 cells constitutively express HIF-2␣ but no HIF-1␣ in normoxia (41). These cells were previously stably transfected with an empty vector (designated 786-0(neo)) or a HA-tagged wild-type VHL (designated 786-0 (HA-VHL)) that re-establishes the oxygen responsiveness of the expression of HIF-2␣ (58) and of the HIF target gene VEGF (66). We found increased amounts of JMJD1A and JMJD2B mRNA in normoxic 786-0(neo) cells compared with 786-0(HA-VHL) cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF

Beyer

Kristensen

Jensen

et al. 2008

Journal of Biological Chemistry

308

301

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Posttranslational histone modifications serve to store epigenetic information and control both nucleosome assembly and recruitment of non-histone proteins. Histone methylation occurs on arginine and lysine residues and is involved in the regulation of gene transcription. A dynamic control of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases. Here we show that the hypoxia-inducible factor HIF-1␣ binds to specific recognition sites in the genes encoding the jumonji family histone demethylases JMJD1A and JMJD2B and induces their expression. Accordingly, hypoxic cells express elevated levels of JMJD1A and JMJD2B mRNA and protein. Furthermore, we find increased expression of JMJD1A and JMJD2B in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of hypoxia-inducible factor. Studies on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program.

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“…Inactivation of the VHL tumor suppressor gene and subsequent loss of function in VHL, and VHL Elongin BC, result in dysfunction in the ubiquitination of hypoxia inducible factor (HIF), which leads to the overexpression of several hypoxia-inducible genes such as vascular endothelial growth factors, erythropoietin, and platelet-derived growth factor, which could explain the development of angiogenic tumors. 7,23,24 The expression of various proteins such as Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2 on the stromal cells suggests an embryonic progenitor cell origin with a hemangioblastic differentiation. Besides these, the interaction of Tie-2 proteins with HIF could be an initiating event in the pathogenesis of the lesions.…”

Section: Discussionmentioning

confidence: 99%

A 10-year retrospective study of hemangioblastomas of the central nervous system with reference to von Hippel–Lindau (VHL) disease

Padhi

Sarangi

Challa

et al. 2011

Journal of Clinical Neuroscience

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Putative Control of Angiogenesis in Hemangioblastomas by the von Hippel-Lindau Tumor Suppressor Gene

Cited by 68 publications

References 0 publications

Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability

The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF

A 10-year retrospective study of hemangioblastomas of the central nervous system with reference to von Hippel–Lindau (VHL) disease

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