HIF1A: Difference between revisions
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<StructureSection load='1H2K' size='340' side='right' caption='Human hypoxia-inducible factor 1 alpha C-terminal activation domain residues 776-829 (mustard) complex with factor inhibiting HIF1 ( grey, green) complex with sulphate, oxalylglycine and Fe+2 (grey) (PDB code [[1h2k]])' scene=''> | |||
<StructureSection load='1H2K' size='340' side='right' caption=' | |||
== Introduction == | == Introduction == | ||
HIF1α is a subunit of the transcription factor HIF1, together with HIF1β <ref name="Neill>O’Neill, Luke A. J., Rigel J. Kishton, and Jeff Rathmell. 2016. “A Guide to Immunometabolism for Immunologists.” Nature Reviews Immunology 16 (9): 553–65. https://doi.org/10.1038/nri.2016.70. | '''HIF1α''' is a subunit of the transcription factor HIF1, together with HIF1β <ref name="Neill>O’Neill, Luke A. J., Rigel J. Kishton, and Jeff Rathmell. 2016. “A Guide to Immunometabolism for Immunologists.” Nature Reviews Immunology 16 (9): 553–65. https://doi.org/10.1038/nri.2016.70. | ||
</ref>. HIF1α is part exclusively of HIF1 whilst HIF1β is part of other transcription factors as well as HIF1. | </ref>. HIF1α is part exclusively of HIF1 whilst HIF1β is part of other transcription factors as well as HIF1. | ||
HIF1 is related to glucose metabolism, stimulation of circulation and it was first described in hypoxia conditions, but it is now known that it can be activated also in normoxia situations, acting especially in the polarization of immune cells to more inflammatory phenotypes <ref name="Neill">. | HIF1 is related to glucose metabolism, stimulation of circulation and it was first described in hypoxia conditions, but it is now known that it can be activated also in normoxia situations, acting especially in the polarization of immune cells to more inflammatory phenotypes <ref name="Neill"</ref>. | ||
The N-terminal region of HIF1α contains a basic helix-loop-helix (bHLH) structure, that is responsible for the interaction with the hypoxia responsive elements (HRE) [5’-(G/C/T)-ACGTGC- (G/T)-3’] present in many enhancers regions of different genes, and a PERARNT-SIM (PAS) domain that are responsible for dimerization with HIF1β. HIF1β is also known as aryl hydrocarbon receptor nuclear translocator (ARNT) <ref name= "Loboda">Loboda, Agnieszka, Alicja Jozkowicz, and Jozef Dulak. 2010. “HIF-1 and HIF-2 Transcription Factors — Similar but Not Identical.” Molecules and Cells 29 (5): 435–42. https://doi.org/10.1007/s10059-010-0067-2.</ref>. | The N-terminal region of HIF1α contains a basic helix-loop-helix (bHLH) structure, that is responsible for the interaction with the hypoxia responsive elements (HRE) [5’-(G/C/T)-ACGTGC- (G/T)-3’] present in many enhancers regions of different genes, and a PERARNT-SIM (PAS) domain that are responsible for dimerization with HIF1β. HIF1β is also known as aryl hydrocarbon receptor nuclear translocator (ARNT) <ref name= "Loboda">Loboda, Agnieszka, Alicja Jozkowicz, and Jozef Dulak. 2010. “HIF-1 and HIF-2 Transcription Factors — Similar but Not Identical.” Molecules and Cells 29 (5): 435–42. https://doi.org/10.1007/s10059-010-0067-2.</ref>. | ||
HIF1α also contains a transactivation domain (TAD) that interacts with CREB binding protein (CBP) and p300, transcription co-activators. In sufficient O2 concentration <ref name="Yang">YANG, Chao, Zhang-Feng ZHONG, Sheng-Peng WANG, Chi-Teng VONG, Bin YU, and Yi-Tao WANG. 2021. “HIF-1: Structure, Biology and Natural Modulators.” Chinese Journal of Natural Medicines 19 (7): 521–27. https://doi.org/10.1016/s1875-5364(21)60051-1. | HIF1α also contains a transactivation domain (TAD) that interacts with CREB binding protein (CBP) and p300, transcription co-activators. In sufficient O2 concentration <ref name="Yang">YANG, Chao, Zhang-Feng ZHONG, Sheng-Peng WANG, Chi-Teng VONG, Bin YU, and Yi-Tao WANG. 2021. “HIF-1: Structure, Biology and Natural Modulators.” Chinese Journal of Natural Medicines 19 (7): 521–27. https://doi.org/10.1016/s1875-5364(21)60051-1. | ||
</ref>, TAD can suffer hydroxylation by prolyl-hydroxylase (PHD) proteins, which inhibits the interaction between those co-activating factors and marks the subunit to ubiquitination by von Hippel-Lindau tumor suppressor protein (VHL), part of the E3 ubiquitin-protein ligase, and consequently degradation in the proteasome. Other interactions with different groups can inhibit the activity of HIF1α as well <ref name="Watts" | </ref>, TAD can suffer hydroxylation by prolyl-hydroxylase (PHD) proteins, which inhibits the interaction between those co-activating factors and marks the subunit to ubiquitination by von Hippel-Lindau tumor suppressor protein (VHL), part of the E3 ubiquitin-protein ligase, and consequently degradation in the proteasome. Other interactions with different groups can inhibit the activity of HIF1α as well <ref name="Watts"/>. | ||
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==References== | ==References== | ||
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