HIF1A

Your Heading Here (maybe something like 'Structure')

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D This is a default text for your page HIF1A. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue. Introduction HIF1α is a subunit of the transcription factor HIF1, together with HIF1β. HIF1α is part exclusively of HIF1 whilst HIF1β is part of other transcription factors as well as HIF1. HIF1 is related to glucose metabolism 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. Structure The N-terminal region of HIF1α contains a basic helix-loop-helix (bHLH) structure and a PERARNT-SIM (PAS) domain that are responsible for dimerization with HIF1β and interaction with the hypoxia responsive elements (HRE) [5’-(G/C/T)-ACGTGC- (G/T)-3’] present in many enhancers regions of different genes. HIF1α also contains a transactivation domain (TAD) that interacts with CREB binding protein (CBP) and p300, transcription co-activators. TAD can suffer hydroxylation that inhibits the interaction between these co-activating factors and marks the subunit to ubiquitination and consequently degradation in the proteasome. A região N-terminal de HIF1α contém uma região de helix-loop-helix básica (bHLH) e um domínio PAS (PERARNT-SIM) que são responsáveis pela dimerização com HIF1β e interação com DNA. HIF-1 reconhece o elemento responsivo a hipóxia (HRE) [5’-(G/C/T)-ACGTGC- (G/T)-3’] presente nos enhancers de muitos genes. A subunidade HIF1α contém dois domínios TAD (transactivation domain) que interagem com CBP (CREB binding protein) e p300, co-ativadores de transcrição na região C-terminal do TAD (CTAD). Essa região sofre hidroxilação o que impede a interação entre os fatores de co-ativação e também marca a subunidade para ubiquitinação e consequente degradação pelo proteassoma. Disease Hypoxia-inducible factors (HIFs) are essential in the progression of various diseases, including cancer and conditions such as peripheral arterial disease, pulmonary arterial hypertension, and sleep apnea. They also play a significant role in regulating insulin signaling and obesity. Under hypoxic conditions, HIFs are stabilized and activate the expression of genes related to cellular adaptation to oxygen deprivation. In the presence of oxygen, HIFs are degraded, but during hypoxia, they form active complexes and promote important cellular changes. Hypoxia is a common feature in solid tumors and their metastases, leading to the activation of HIFs, which influence gene expression in both tumor cells and immune cells in the tumor microenvironment. This affects tumor progression and treatment response. In particular, HIF-1α is crucial in the initiation of certain types of cancer, such as clear cell renal cell carcinoma (ccRCC), and is elevated in pre-neoplastic stages. Structural highlights This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

Alves, Cinthia C, Eduardo A Donadi, and Silvana Giuliatti. 2021. “Structural Characterization of the Interaction of Hypoxia Inducible Factor-1 with Its Hypoxia Responsive Element at the −964G > a Variation Site of the HLA-G Promoter Region.” International Journal of Molecular Sciences 22 (23): 13046–46. https://doi.org/10.3390/ijms222313046.

Proteopedia Page Contributors and Editors (what is this?)

Bruno Prado Eleuterio, Michal Harel, Milena Grigoriou