Regulation of HIF-1α Stability through S-Nitrosylation

Li, Fang; Sonveaux, Pierre; Rabbani, Zahid N.; Liu, Shanling; Yan, Bin; Huang, Qian; Vujašković, Željko; Dewhirst, Mark W.; Li, Chuan-Yuan

doi:10.1016/j.molcel.2007.02.024

Cited by 401 publications

(373 citation statements)

References 51 publications

Supporting

Mentioning

354

Contrasting

Unclassified

Order By: Relevance

“…HIF1 has been referred to as the "master regulator of oxygen homeostasis" 7 , but it is regulated by many factors aside from hypoxia, including oncogenes, growth factors and free radicals [27][28][29] . Free radicals are chemical species that contain unpaired electrons; of particular importance here are oxygen-containing radicals, such as the superoxide anion (O 2 -).…”

Section: Regulation Of Hif1 By Free Radicalsmentioning

confidence: 99%

“…Exposure to NO has been shown to nitrosylate thiols in the HIF1α protein leading to HIF1α stabilization under aerobic conditions 39 . Recently, the specific target has been identified to be a cysteine residue in the ODD of HIF1α, which blocks its binding to the VHl complex for subsequent degradation 27 . NO can promote binding of HIF1 to HREs in HIF1 target genes by binding to an adjacent HIF1 ancillary sequence (HAs) and hence acting as a transcriptional co-activator 40 .…”

Section: Free Radical Regulation Of Hif1 Under Aerobic Conditionsmentioning

confidence: 99%

See 1 more Smart Citation

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

2008

View full text Add to dashboard Cite

Hypoxia and free radicals, such as reactive oxygen and nitrogen species, can alter the function and/or activity of the transcription factor hypoxia-inducible factor 1 (HIF1). Interplay between free radicals, hypoxia and HIF1 activity is complex and can influence the earliest stages of tumour development. The hypoxic environment of tumours is heterogeneous, both spatially and temporally, and can change in response to cytotoxic therapy. Free radicals created by hypoxia, hypoxia-reoxygenation cycling and immune cell infiltration after cytotoxic therapy strongly influence HIF1 activity. HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit.Virchow first described the abnormal structure of tumour vessels using contrast agents in human tumours as early as the mid 1800s 1 . A few decades later, Goldman was among the first to suggest that angiogenesis was associated with tumour growth 2 . A number of other investigators in the nineteenth and early twentieth centuries evaluated tumour angiogenesis, using techniques such as microangiography, vascular casting and window chamber models. Warren has reviewed this early work in great detail 3 . Folkman illuminated the crucial role of tumour angiogenesis by hypothesizing that tumour growth was dependent upon angiogenesis and that, if angiogenesis could be inhibited, it could maintain tumour deposits in a quiescent state 4 . These early works set the stage for the concept that tumours require angiogenesis to provide a nutrient supply. Although it is well-established that angiogenesis occurs in nearly all human solid tumours, it does not occur in an efficient manner, leading to spatial and temporal inadequacies in delivery of oxygen and other nutrients. These inefficiencies in nutrient delivery lead to a brutal cycle of unsatisfied demand by the tumour, which drives continued aberrant angiogenesis.The transcription factor hypoxia-inducible factor 1 (HIF1) plays an important part in tumour progression by upregulating genes that control angiogenesis, meta-stasis and resistance to oxidative stress. It also controls the switch to anaerobic metabolism, which can maintain cell NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript viability under hypoxic conditions. Further, HIF1 activity can promote treatment resistance by promoting endothelial and tumour cell survival after cytotoxic therapy. The mechanisms that control HIF1 activity are complex and are influenced by microenvironmental factors involving hypoxia, oxidative and nitrosative stress.In this Review we will discuss four important and interrelated aspects of tumour hypoxia. First, we will define the hypoxic response, discussing its relevance in influencing tumour cell survival, behaviour and angiogenesis. We will examine the physiological factors that contribute to hypoxia, emphasizing a perspective based on spatial and temporal dysfunction of tumour microcirculation. The question of whethe...

show abstract

Section: Regulation Of Hif1 By Free Radicalsmentioning

confidence: 99%

Section: Free Radical Regulation Of Hif1 Under Aerobic Conditionsmentioning

confidence: 99%

Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

2008

View full text Add to dashboard Cite

show abstract

“…Many proteins that are reported to be regulated by S-nitrosothiol formation in the cardiovascular system have also been shown, most often previously, to be regulated by disulfides, often at the same cysteine residue. For example, S-nitrosation and disulfide formation has been shown to induce the same functional change in hypoxia-inducible factor 1α-subunit [92,93], caspase-3 [60,94], Na + /K + ATPase [95,96] and actin [84,97]. A summary of proteins that form S-nitrosothiols as well as disulfides is provided in Table 1, some of which are discussed in more detail below.…”

Section: Is No-dependent Signal Transduction Mediated By Stable S-nitmentioning

confidence: 99%

How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?

Wolhuter

Eaton

2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Over the last 25 years protein S-nitrosylation, also known more correctly as S-nitrosation, has been progressively implicated in virtually every nitric oxide-regulated process within the cardiovascular system. The current, widely-held paradigm is that S-nitrosylation plays an equivalent role as phosphorylation, providing a stable and controllable post-translational modification that directly regulates end-effector target proteins to elicit biological responses. However, this concept largely ignores the intrinsic instability of the nitrosothiol bond, which rapidly reacts with typically abundant thiol-containing molecules to generate more stable disulfide bonds. These protein disulfides, formed via a nitrosothiol intermediate redox state, are rationally anticipated to be the predominant endeffector modification that mediates functional alterations when cells encounter nitrosative stimuli. In this review we present evidence and explain our reasoning for arriving at this conclusion that may be controversial to some researchers in the field.

show abstract

“…Although studies have shown that BMDCs increasingly infiltrate into tumours after irradiation and facilitate relapse 3–5 , they do not incorporate into the vasculature. Thus, these BMDCs do not participate in vasculogenesis as defined by Begg and colleagues and in the literature in general 1,6 .…”

mentioning

confidence: 99%

“…Thus, these BMDCs do not participate in vasculogenesis as defined by Begg and colleagues and in the literature in general 1,6 . Indeed, the BMDCs that are recruited by irradiated tumours are generally of myeloid lineage — including ‘alternatively’ activated macrophages and tyrosine protein kinase receptor (TIE2)-expressing monocytes (TEMs) — that facilitate post-irradiation tumour revascularization through paracrine mechanisms 2–5 . Distorting the definition of vasculogenesis not only confuses the literature but also misrepresents the biology — in this case by implying that the cells are doing something that they are not.…”

mentioning

confidence: 99%