Targeting Protein–Protein Interactions in the HIF System

Wilkins, Sarah E.; Abboud, Martine I.; Hancock, Rebecca L.; Schofield, Christopher J.

doi:10.1002/cmdc.201600012

Cited by 73 publications

(54 citation statements)

References 145 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recent discovery that the HIF1 PAS domains, like the HIF2 PAS domain, contain hydrophobic pockets should stimulate efforts to identify direct HIF1 antagonists (Wu et al Nature 2015). In addition, acriflavine and proflavine were identified in a phenotypic screen for HIF1 inhibitors and appear to target a HIF1α/ARNT interface (Wilkins et al, 2016). Many other compounds have been identified that can, at least indirectly, downregulate HIF1 (Xia et al, 2012).…”

Section: Pharmacological Inhibition Of Hifmentioning

confidence: 99%

The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks

2017

View full text Add to dashboard Cite

SUMMARY The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets, the HIFα subunits, represent the core of an ancient oxygen-monitoring machinery used by metazoans. In this review we highlight recent progress in understanding the overlapping versus specific roles of EGLN enzymes and HIF isoforms and discuss how feedback loops based on recently identified noncoding RNAs introduce additional layers of complexity to the hypoxic response. Based on novel interactions identified upstream and downstream of EGLNs, an integrated network connecting oxygen-sensing functions to metabolic and signaling pathways is gradually emerging with broad therapeutic implications.

show abstract

Section: Pharmacological Inhibition Of Hifmentioning

confidence: 99%

The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks

2017

View full text Add to dashboard Cite

show abstract

“…In addition to the critical subunit dimerization between HIF-α and ARNT, the direct interactions of HIF-α with other regulatory proteins (e.g. those shown in Figure 3) have also been targeted to modulate HIF activities in different therapeutic settings [38]. …”

Section: Interactions Between Hif-1α and Other Macromoleculesmentioning

confidence: 99%

Structural characterization of mammalian bHLH-PAS transcription factors

Rastinejad

2017

Current Opinion in Structural Biology

View full text Add to dashboard Cite

The mammalian basic helix-loop-helix-PER-ARNT-SIM (bHLH–PAS) transcription factors share common architectural features that include a bHLH DNA-binding domain and tandemly positioned PAS domains. The sixteen members of this family include the hypoxia-inducible factors (HIF-1α and HIF-2α), ARNT (also known as HIF-1β), CLOCK and BMAL1. Most bHLH-PAS proteins have been genetically linked to variety of diseases in humans, including cancers, metabolic syndromes and psychiatric conditions. To function as transcription factors, the bHLH-PAS proteins must form heterodimeric complexes. Recent crystallographic studies of HIF-α-ARNT and CLOCK-BMAL1 complexes have unveiled the organization of their multi-domain bHLH-PAS-A-PAS-B segments, revealing how these architectures can give rise to unique patterns of heterodimerization. As our structural understanding becomes better integrated with ligand-discovery and target gene identification, a more comprehensive picture of their architectural and functional properties will emerge.

show abstract

“…High expression of HIF‐1 α is significantly associated with radio‐resistance 33. Up to date, there are few studies on the relationship between DNA methylation of oxygenation‐related gene and radio‐sensitivity.…”

Section: Radio‐sensitivity and Dna Methylation Of Re‐oxygenation‐relamentioning

confidence: 99%

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

et al. 2018

View full text Add to dashboard Cite

Radiotherapy is an important modality for treatment of carcinomas; however, radio‐resistance is still a difficult problem. Aberrant epigenetic alterations play an important role in cancer development. Among epigenetic parameters, DNA methylation has arguably attracted the most attention in the radio‐resistance process. To determine the role of DNA methylation in radiation resistance, several studies were conducted. We summarized previous studies on the role of DNA methylation in radiotherapy. We observed this significant role of DNA methylation in genes related to DNA repair, cell proliferation, cell cycle process, and re‐oxygenation. Furtherly, we also conclude the predictive effect of DNA methylation on tumor radio‐sensitivity and the using of DNA methyltransferase inhibitors in clinical practice. DNA methylation plays a pivotal role in the radio‐sensitivity of tumor radio‐therapy. While hyper‐methylation or hypo‐methylation of genes is related to gene functions.

show abstract

Targeting Protein–Protein Interactions in the HIF System

Cited by 73 publications

References 145 publications

The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks

The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks

Structural characterization of mammalian bHLH-PAS transcription factors

The pivotal role of DNA methylation in the radio‐sensitivity of tumor radiotherapy

Contact Info

Product

Resources

About