<i>S</i>‐nitrosation of Cys‐800 of HIF‐1α protein activates its interaction with p300 and stimulates its transcriptional activity

Yasinska, Inna M.; Sumbayev, Vadim V.

doi:10.1016/s0014-5793(03)00807-x

Cited by 147 publications

(112 citation statements)

References 28 publications

(30 reference statements)

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“…This was postulated to occur via enhancement of the interaction between the CAD and CBP/p300, thus linking cellular redox status to recruitment of CBP to HIF. 56 However, more recent quantitative interaction studies with purified proteins and peptides demonstrated a significant decrease in p300 binding upon Cys800 S-nitrosylation. 41 SUMOylation of HIF-1a has also been described by several groups, however the reported outcomes of this modification are varied.…”

Section: Other Modifications Affecting Hif-driven Transcriptionmentioning

confidence: 99%

Turn me on: regulating HIF transcriptional activity

2008

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The hypoxia-inducible factors (HIFs) are critical for cellular adaptation to limiting oxygen and regulate a wide array of genes when cued by cellular oxygen-sensing mechanisms. HIF is able to direct transcription from either of two transactivation domains, each of which is regulated by distinct mechanisms. The oxygen-dependent asparaginyl hydroxylase factor-inhibiting HIF-1a (FIH-1) is a key regulator of the HIF C-terminal transactivation domain, and provides a direct link between oxygen sensation and HIFmediated transcription. Additionally, there are phosphorylation and nitrosylation events reported to modulate HIF transcriptional activity, as well as numerous transcriptional coactivators and other interacting proteins that together provide cell and tissue specificity of HIF target gene regulation. The maintenance of oxygen homeostasis is a crucial physiological requirement that involves coordinated regulation of a plethora of genes. The hypoxia-inducible transcription factors (HIFs) are responsible for a major genomic response to hypoxia, where cellular oxygen demand exceeds supply. The HIFs directly regulate the transcription of more than 70 genes involved in cellular processes that act to directly address this deficit by decreasing oxygen dependence and consumption by cells, and by increasing the efficiency of oxygen delivery to cells. These processes include vasculogenesis and angiogenesis, metabolism, vasodilation, cell migration, signalling and cell fate decisions. As such, the HIFs are fundamental to embryonic development and the pathophysiology of many serious human diseases, and are therefore subject to strict regulatory mechanisms that act to limit transcriptional activity to periods of cellular oxygen stress. The HIF proteins are subject to oxygen-dependent regulation, both at the level of protein stability (reviewed in this issue by R Bruick) and transcriptional activity, rendering them almost inactive at normoxia, but potently inducible in hypoxia. The regulation of the transcriptional activity of the HIF proteins, both via oxygen-dependent and oxygen-independent mechanisms, will be discussed in this review. The HIFsHIF is assembled from a-and b-subunits to become a transcriptionally active heterodimer. 1 Both subunits are members of the bHLH/PAS (basic helix-loop-helix/Per-ArntSim homology) family of transcription factors, and both contain transactivation domains (Figure 1). 2,3 Whereas HIF1b, also known as the aryl hydrocarbon receptor nuclear translocator (Arnt1), is a constitutively expressed nuclear protein, the a-subunit is strictly regulated in an oxygendependent manner. There are three paralogues of the HIF-a subunit, HIF-1a, HIF-2a and HIF-3a, and three paralogues of HIF-1b (Arnt1, Arnt2 and Arnt3), with either HIF-1a or HIF-2a being able to heterodimerize with HIF-1b to form the functional HIF transcription factor complexes responsible for the hypoxic shift in gene expression. HIF-3a has no known role as an active transcription factor, and is instead postulated to behave as a negative reg...

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Section: Other Modifications Affecting Hif-driven Transcriptionmentioning

confidence: 99%

Turn me on: regulating HIF transcriptional activity

2008

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“…Hypoxia-inducible factor (HIF)1α also is regulated in a redox dependent manner, and its degradation and activation are regulated via cysteine oxidation. S-nitrosylation of HIF1α promotes its stabilization [205], and S-nitrosylation of Cys-800 activates HIF1α-p300 interaction and stimulates protein transactivation [206].…”

Section: Redox Regulation Of Transcription Factorsmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

698

652

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“…Additionally, nitric oxide (NO) signaling induces covalent modification of HIF-1 protein. NO stimulates S-nitrosation of cysteine 800, a critical residue within the C-TAD of HIF-1α, which enhances interaction of HIF-1 with p300/CBP and increases HIF-1 activity [42,43].…”

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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S‐nitrosation of Cys‐800 of HIF‐1α protein activates its interaction with p300 and stimulates its transcriptional activity

Cited by 147 publications

References 28 publications

Turn me on: regulating HIF transcriptional activity

Turn me on: regulating HIF transcriptional activity

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

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

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