ArticleCell death and differentiation2011
Involvement of BH4 domain of bcl-2 in the regulation of HIF-1-mediated VEGF expression in hypoxic tumor cells.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 68 citations in OpenAlex.
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- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Anti-apoptotic protein Bcl-2 contributes to the determination of reserve cells during myogenic differentiation of C2C12 cells.In vitro cellular & developmental biology. Animal · 2024Article
- Bcl-2 dependent modulation of Hippo pathway in cancer cells.Cell communication and signaling : CCS · 2024Article
- Dormancy of cutaneous melanoma.Cancer cell international · 2024Review
- Targeting the anti-apoptotic Bcl-2 family proteins: machine learning virtual screening and biological evaluation of new small molecules.Theranostics · 2022Article
- Effects of Hypoxia-Inducible Factor 1 (HIF-1) Signaling Pathway on Acute Ischemic Stroke.Computational and mathematical methods in medicine · 2022Article
- The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication.Frontiers in physiology · 2022Article
- Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2.Pharmaceutics · 2022Review
- miR-519d-3p suppresses tumorigenicity and metastasis by inhibiting Bcl-w and HIF-1α in NSCLC.Molecular therapy oncolytics · 2021Article
- Hypoxia-dependent drivers of melanoma progression.Journal of experimental & clinical cancer research : CR · 2021Review
- The evolving landscape of NMolecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Melanoma-specific bcl-2 promotes a protumoral M2-like phenotype by tumor-associated macrophages.Journal for immunotherapy of cancer · 2020Article
- Targeting hypoxia in tumor: a new promising therapeutic strategy.Journal of experimental & clinical cancer research : CR · 2020Article
- Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis.Scientific reports · 2019Article
- MiT/TFE Family of Transcription Factors, Lysosomes, and Cancer.Annual review of cancer biology · 2019Article
- The correlation of the expressions of WWOX, LGR5 and vasohibin-1 in epithelial ovarian cancer and their clinical significance.International journal of clinical and experimental pathology · 2019Article
- Microarray analysis of the molecular mechanisms associated with age and body mass index in human meniscal injury.Molecular medicine reports · 2019Article
- Analysis of regulator of G-protein signalling 2 (RGS2) expression and function during prostate cancer progression.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In addition to act as an antiapoptotic protein, B-cell lymphoma (bcl)-2 can also promote tumor angiogenesis. In this context, we have previously demonstrated that under hypoxia bcl-2 promotes hypoxia-inducible factor-1 (HIF-1)-mediated vascular endothelial growth factor (VEGF) expression in melanoma and breast carcinoma. Here, we report on the role of the BH4 domain in bcl-2 functions, by showing that removal of or mutations at the BH4 domain abrogate the ability of bcl-2 to induce VEGF protein expression and transcriptional activity under hypoxia in human melanoma cells. We have also extended this observation to other human tumor histotypes, such as colon, ovarian and lung carcinomas. The involvement of BH4 on HIF-1α protein expression, stability, ubiquitination and HIF-1 transcriptional activity was also demonstrated in melanoma experimental model. Moreover, we validated the role of the BH4 domain of bcl-2 in the regulation of HIF-1/VEGF axis, demonstrating that BH4 peptide is sufficient to increase HIF-1α protein half-life impairing HIF-1α protein ubiquitination, and to enhance VEGF secretion in melanoma cells exposed to hypoxia. Finally, we found that the mechanism by which bcl-2 regulates HIF-1-mediated VEGF expression does not require BH1 and BH2 domains, and it is independent of antiapoptotic and prosurvival function of bcl-2.
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