Role of CBP in regulating HIF-1-mediated activation of transcription

Ruas, Jorge L.; Poellinger, Lorenz; Pereira, Teresa

doi:10.1242/jcs.01617

Cited by 86 publications

(67 citation statements)

References 69 publications

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“…This result is consistent with the knowledge that MEK/ERK is involved in the transcriptional activity of HIF1 by phosphorylating the HIF-1 cofactor p300/CEB (36), which is required for the transcriptional activities of HIF-1 (46,47). Additionally, MEK/ ERK-mediated cell signaling is important for phosphorylation of c-fos, which is a component of the AP1 transcription factor, another important regulator of VEGF expression.…”

Section: Discussionsupporting

confidence: 91%

Requirement of hypoxia-inducible factor-1α down-regulation in mediating the antitumor activity of the anti–epidermal growth factor receptor monoclonal antibody cetuximab

Lü

Liang

et al. 2008

Molecular Cancer Therapeutics

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We tested our novel hypothesis that down-regulation of hypoxia-inducible factor-1A (HIF-1A), the regulated subunit of HIF-1 transcription factor that controls gene expression involved in key functional properties of cancer cells (including metabolism, survival, proliferation, invasion, angiogenesis, and metastasis), contributes to a major antitumor mechanism of cetuximab, an approved therapeutic monoclonal antibody that blocks activation of the epidermal growth factor receptor. We showed that cetuximab treatment down-regulates HIF-1A levels by inhibiting synthesis of HIF-1A rather than by enhancing degradation of the protein. Inhibition of HIF-1A protein synthesis was dependent on effective inhibition of the phosphoinositide-3 kinase (PI3K)/Akt pathway by cetuximab, because the inhibition was prevented in cells transfected with a constitutively active PI3K or a constitutively active Akt but not in cells with a constitutively active MEK. Overexpression of HIF-1A conferred cellular resistance to cetuximab-induced apoptosis and inhibition of vascular endothelial growth factor production in sensitive cancer cell models, and expression knockdown of HIF-1A by RNA interference substantially restored cellular sensitivity to the cetuximab-mediated antitumor activities in experimental resistant cell models created by transfection of an oncogenic Ras gene (G12V) or by concurrent treatment of the cells with insulin-like growth factor-I. In summary, our data show that cetuximab decreases HIF-1A protein synthesis through inhibition of a PI3K-dependent pathway and that an effective down-regulation of HIF-1A is required for maximal therapeutic effects of cetuximab in cancer cells.

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Section: Discussionsupporting

confidence: 91%

Requirement of hypoxia-inducible factor-1α down-regulation in mediating the antitumor activity of the anti–epidermal growth factor receptor monoclonal antibody cetuximab

Lü

Liang

et al. 2008

Molecular Cancer Therapeutics

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“…SRC-1 interacts with a variety of nuclear receptors in a hormone-dependent manner, and is thought to play a role in bridging the activated receptor with basal transcription machinery, as well as acetylating histones [31]. CBP mediates colocalization of HIF-1 and SRC-1 [38], presumably by the complex formed between CBP/p300 and SRC-1, which amplifies CBP/ p300-mediated activation of HIF-1 responsive promoters [31,39]. While all three of these HATs enhance HIF-1 function, there are few reports of investigators directly analyzing histone acetylation at the promoters of HIF-1 target gene.…”

Section: Regulation Of Gene Expression Through Covalent Modification mentioning

confidence: 99%

Hypoxia-induced and stress-specific changes in chromatin structure and function

Johnson

Barton

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Cellular adaptation to stress relies on specific, regulated responses to evoke changes in gene expression. Stresses such as hypoxia, heat shock, oxidative stress and DNA-damage activate signaling cascades that ultimately lead to either induction or repression of stress-responsive genes. In this review, we concentrate on the mechanisms by which stress-induced signaling promotes alterations in chromatin structure, whether the read-out is activation or repression of transcription. Specific alterations in chromatin are highly regulated and dictated by the type of imposed stress. Our primary focus is on the types of chromatin alterations that occur under hypoxic conditions, which exist within a majority of tumors, and to compare these to changes in chromatin structure that occur in response to a wide variety of cellular stresses.

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“…SRC-1 is a HIF-1 transcriptional coactivator in normoxic and hypoxic cells (26,32) whereas SIRT-1 deacetylase, exerts SRC-1 opposing effects in the androgen receptor signalling pathway in prostate cancer cells (33) and has been linked to hypoxia-mediated transcription (34). Given the functional and physical interplay of SRC-1 and SIRT-1 with HIF-1α (26,32,35) together with the identification of multiple putative HREs in the regulatory region of the CXCR4 promoter triggered our interest to investigate the effect of these two factors on the activity of CXCR4 promoter in hypoxic breast cancer cells. To assess the role of SRC-1 and SIRT-1 on CXCR4 promoter activity under hypoxia mimicking conditions, we performed luciferase reporter assays in MCF-7 cells transfected with the CXCR4-luc reporter and exogenously expressing either SRC-1 or SIRT-1 under normoxic or hypoxia mimicking conditions.…”

Section: Hif-1α Recruitment To the Regulatory Regions Of The Promotermentioning

confidence: 99%

“…Previous work in our laboratory has indicated that the p300/CBP associated factor (PCAF) is a crucial coordinator of the action of both p53 and HIF-1α in hypoxic cancer cells (22). PCAF, p300 and members of the p160 family of the nuclear hormone receptor (NR) co-activators, such as the steroid receptor co-activator 1 (SRC-1), bear intrinsic histone acetyl transferase (HAT) activity thereby modulating directly or indirectly the transcriptional activity of both HIF-1α and p53 (22,25,26). On the contrary, members of the NAD + -dependent deacetylase (HDAC) family of sirtuins, such as SIRT-1, antagonise HAT activity and target p53 and HIF-1α for deacetylation in mammalian cells (27).…”

Section: Introductionmentioning

confidence: 99%

Regulation of CXCR4 gene expression in breast cancer cells under diverse stress conditions

Andreou

Rajendran

Krstic‐Demonacos

et al. 2012

International Journal of Oncology

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Abstract. Chronic inflammation is a critical component in breast cancer progression. Pro-inflammatory mediators along with growth/survival factors within the tumor microenvironment potentiate the expression of pro-inflammatory cytokines (IL-1, IL-6, TNF-α), chemotactic cytokines and their receptors (CXCR4, CXCL12, CXCL8) and angiogenic factors (VEGF) that often overcome the effect of anti-inflammatory molecules (IL-4, IL-10) thus evading the host's antitumor immunity. Detailed knowledge, therefore, of the regulatory mechanisms determining cytokine levels is essential to understand the pathogenesis of breast cancer. HIF-1α and NF-κB transcription factors are important players for the establishment of a pro-inflammatory and potentially oncogenic environment. HIF-1α is the key mediator of the cellular response to oxygen deprivation and induces the expression of genes involved in survival and angiogenesis within solid hypoxic tumors. The expression of these genes is often modulated by the p53 tumor suppressor protein that induces apoptosis or cell cycle arrest in neoplastic cells. Functional crosstalk between HIF-1α and p53 pathways mediated by modulators shared between the two transcription factors such as SRC-1 and SIRT-1 differentially regulate the expression of distinct subsets of their target genes under variable stress conditions. In an attempt to shed light on the complex regulatory mechanisms involved in cancer-related inflammation, we investigated the role of the two common p53 and HIF-1α co-regulators SRC-1 and SIRT-1, in the expression of the highly potent metastatic chemokine receptor CXCR4. Both SRC-1 and SIRT-1 overexpression in DSFX-treated MCF-7 cells reduced CXCR4 cellular levels implying that both co-regulators are crucial factors in the determination of the metastatic potential of breast cancer cells.

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Role of CBP in regulating HIF-1-mediated activation of transcription

Cited by 86 publications

References 69 publications

Requirement of hypoxia-inducible factor-1α down-regulation in mediating the antitumor activity of the anti–epidermal growth factor receptor monoclonal antibody cetuximab

Requirement of hypoxia-inducible factor-1α down-regulation in mediating the antitumor activity of the anti–epidermal growth factor receptor monoclonal antibody cetuximab

Hypoxia-induced and stress-specific changes in chromatin structure and function

Regulation of CXCR4 gene expression in breast cancer cells under diverse stress conditions

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