Specific Inhibition of HIF Activity: Can Peptides Lead the Way?
Reduced oxygen availability (hypoxia) is a characteristic of many disorders including cancer. Central components of the systemic and cellular response to hypoxia are the Hypoxia Inducible Factors (HIFs), a small family of heterodimeric transcription factors that directly or indirectly regulate the e...
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doaj-c3a48587538b4df2b1afdf4a983ef4aa2021-01-23T00:03:53ZengMDPI AGCancers2072-66942021-01-011341041010.3390/cancers13030410Specific Inhibition of HIF Activity: Can Peptides Lead the Way?Ilias Mylonis0Georgia Chachami1George Simos2Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceLaboratory of Biochemistry, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceLaboratory of Biochemistry, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceReduced oxygen availability (hypoxia) is a characteristic of many disorders including cancer. Central components of the systemic and cellular response to hypoxia are the Hypoxia Inducible Factors (HIFs), a small family of heterodimeric transcription factors that directly or indirectly regulate the expression of hundreds of genes, the products of which mediate adaptive changes in processes that include metabolism, erythropoiesis, and angiogenesis. The overexpression of HIFs has been linked to the pathogenesis and progression of cancer. Moreover, evidence from cellular and animal models have convincingly shown that targeting HIFs represents a valid approach to treat hypoxia-related disorders. However, targeting transcription factors with small molecules is a very demanding task and development of HIF inhibitors with specificity and therapeutic potential has largely remained an unattainable challenge. Another promising approach to inhibit HIFs is to use peptides modelled after HIF subunit domains known to be involved in protein–protein interactions that are critical for HIF function. Introduction of these peptides into cells can inhibit, through competition, the activity of endogenous HIFs in a sequence and, therefore also isoform, specific manner. This review summarizes the involvement of HIFs in cancer and the approaches for targeting them, with a special focus on the development of peptide HIF inhibitors and their prospects as highly-specific pharmacological agents.https://www.mdpi.com/2072-6694/13/3/410hypoxiaHIFHIF-1αHIF inhibitionpeptide inhibitors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ilias Mylonis Georgia Chachami George Simos |
spellingShingle |
Ilias Mylonis Georgia Chachami George Simos Specific Inhibition of HIF Activity: Can Peptides Lead the Way? Cancers hypoxia HIF HIF-1α HIF inhibition peptide inhibitors |
author_facet |
Ilias Mylonis Georgia Chachami George Simos |
author_sort |
Ilias Mylonis |
title |
Specific Inhibition of HIF Activity: Can Peptides Lead the Way? |
title_short |
Specific Inhibition of HIF Activity: Can Peptides Lead the Way? |
title_full |
Specific Inhibition of HIF Activity: Can Peptides Lead the Way? |
title_fullStr |
Specific Inhibition of HIF Activity: Can Peptides Lead the Way? |
title_full_unstemmed |
Specific Inhibition of HIF Activity: Can Peptides Lead the Way? |
title_sort |
specific inhibition of hif activity: can peptides lead the way? |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-01-01 |
description |
Reduced oxygen availability (hypoxia) is a characteristic of many disorders including cancer. Central components of the systemic and cellular response to hypoxia are the Hypoxia Inducible Factors (HIFs), a small family of heterodimeric transcription factors that directly or indirectly regulate the expression of hundreds of genes, the products of which mediate adaptive changes in processes that include metabolism, erythropoiesis, and angiogenesis. The overexpression of HIFs has been linked to the pathogenesis and progression of cancer. Moreover, evidence from cellular and animal models have convincingly shown that targeting HIFs represents a valid approach to treat hypoxia-related disorders. However, targeting transcription factors with small molecules is a very demanding task and development of HIF inhibitors with specificity and therapeutic potential has largely remained an unattainable challenge. Another promising approach to inhibit HIFs is to use peptides modelled after HIF subunit domains known to be involved in protein–protein interactions that are critical for HIF function. Introduction of these peptides into cells can inhibit, through competition, the activity of endogenous HIFs in a sequence and, therefore also isoform, specific manner. This review summarizes the involvement of HIFs in cancer and the approaches for targeting them, with a special focus on the development of peptide HIF inhibitors and their prospects as highly-specific pharmacological agents. |
topic |
hypoxia HIF HIF-1α HIF inhibition peptide inhibitors |
url |
https://www.mdpi.com/2072-6694/13/3/410 |
work_keys_str_mv |
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