Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

By Y. Makino, R. Cao, K. Svensson, G. Bertilsson, Mikael Asman, Hirotoshi Tanaka, Yihai Cao, A. Berkenstam, L. Poellinger. Nature, 2001

764 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/8570fb6e3683b851d7e6d3dcdb74cc4fa57bbf41

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In Cancer Research

1. G. Semenza
2. P. Ratcliffe
3. W. Kaelin
4. J. Pouysségur
5. J. Chiche
6. M. Brahimi-Horn
7. V. Haase
8. Richard J. Johnson

In Molecular Biology

1. G. Semenza
2. P. Ratcliffe
3. W. Kaelin
4. J. Chiche
5. J. Pouysségur
6. M. Brahimi-Horn
7. J. Espinosa
8. V. L. Dengler

In Physiology

1. G. Semenza
2. P. Ratcliffe
3. J. Pouysségur
4. W. Kaelin
5. Roland H. Wenger
6. J. Chiche
7. Richard J. Johnson
8. M. Brahimi-Horn

Citations in the corpus

• Transcriptional Regulation by Hypoxia Inducible Factors (2013, background): “Although identified via homology searches for additional bHLH-PAS and HIF-related proteins, the third known alpha subunit, HIF3A, displays less similarity as well as distinct functional characteristics compared to HIF1A and HIF2A (Gu et al., 1998; Makino et al., 2001).”
• The role of hypoxia-inducible factors in tumorigenesis (2008, background): “HIF-3a mRNA can be detected in a variety of tissues, including the thymus, lung, brain, heart, kidney, liver, eye, and brain.(12,13)”
• The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer (2008, background): “However, transcriptional activation by HIF3α has not been well documented and some HIF3α splice variants clearly inhibit HIF-dependent transcriptional activatio”
• Regulation of erythropoiesis by hypoxia-inducible factors (2013, background): “WhereasHIF-1 andHIF-2 heterodimers function as transcriptional activators, splice variants of HIF-3α have been shown to be inhibitory.(66,67) Although HIF-1 and HIF-2 sharemany transcriptional targets, certain genes and processes do not appear to be co-regulated.”
• Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. (2005, background): “HIF-3 -2, also called inhibitory PAS domain protein (IPAS), binds to HIF-1 and prevents the formation of a functional HIF-1 / complex, and it thus prevents HIF target gene activation (Makino et al., 2001).”
• Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. (2008, background): “The most clearly defined of these is antagonism of HREmediated transcription by an alternatively promoted and spliced product termed IPAS that binds HIF1a to create inactive heterodimers (Makino et al., 2001).”
• Cellular adaptation to hypoxia: O2‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O2‐regulated gene expression (2002, background): “A novel inhibitory PAS protein (IPAS), a splice variant of HIF-3 , has recently been discovered by Poellinger and co-workers (26).”
• Hypoxia: A key regulator of angiogenesis in cancer (2007, background): “In contrast, iPAS, a splice variant of HIF-3α, is involved in negative regulation of HIF-1α transcriptional activity; it is expressed in the cornea of the eye, the cerebellum, and cerebrum [18].”
• HIF-1 as a target for drug development (2003, background): “Another mechanism of regulating HIF-1 is the inhibition of HIF-1α and HIF-1β dimerization, which is achieved through competitive binding of an inhibitory PAS (IPAS) molecul”
• Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer (2009, background): “Little is known about HIF-3 , which can act as a dominant negative of HIF transcriptional activity [110].”