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What is HIF-1?

Improving glucose control in people with diabetes increases HIF-1[alpha] protein and has wide-ranging benefits, some of which are at least partially mediated by HIF-1[alpha]. Nevertheless, most strategies to improve diabetes or its complications via regulation of HIF-1[alpha] have not currently proven to be clinically useful.

What is HIF-1a (hypoxia-inducible factor 1 alpha)?

Abstract. Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O2 levels) is a common character in …

What are the different types of HIF signaling pathways?

Dickau 4 (Tang, 2003), where health information is defined as information pertaining to the health of an individual or health care provided to an individual (Tang, 2003), immediate electronic access to person- and population-level information by authorized, and only authorized, users (Tang, 2003), provision of knowledge and decision-support that enhance the quality, safety, and …

How does HIF-1 respond to systemic oxygen levels?

HIF-1 alpha is stabilised only at O 2 concentrations below 5%. Under normoxic conditions HIF-1 alpha has a short half-life and may be degraded within 5-8 minutes in both nuclear and cytoplasmic compartments (PMID: 11454738). Therefore, proper sample preparation is critical to aiding WB success. If care hasn’t been taken with

How does HIF-1 alpha work?

Under hypoxic conditions, Hif-1 alpha translocates to the cell nucleus and associates with Hif-1 beta. This complex then binds to the HRE region of the DNA resulting in the transcription of genes that are involved in a multitude of processes including erythropoesis, glycolysis, and angiogenesis.

How is HIF-1 activated?

Insulin likewise activates HIF-1α by activating multiple protein kinases necessary for expression and function [37]. In another study on HIF-1 activation, homozygous deletion of the p53 gene led to HIF-1 activation [38]. Therefore, p53, responsible for promoting ubiquitination of HIF-1α, may be another possible target.

How does HIF increase performance through angiogenesis?

The target genes of HIF-1 increase oxygen transport through mechanisms such as erythropoietin-mediated erythropoiesis and vascular endothelial growth factor-induced angiogenesis and improve tissue function during low oxygen availability through increased expression of glucose transporters and glycolytic enzymes, which ...Sep 22, 2015

Where is HIF 1a expressed?

In hemangioblastoma, HIF1A expression is found in most cells sampled from the well-vascularized tumor. Although in both renal carcinoma and hemangioblastoma, the von Hippel-Lindau gene is inactivated, HIF1A is still expressed at high levels.

What is the HIF pathway?

Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis.

How is HIF-1 regulated?

Under normal oxygen tension, HIF-1α protein expression is negatively regulated by proteasomal degradation and ubiquitination in a pathway involving von Hippel−Lindau protein (pVHL), a tumor suppressor protein and one of the recognized components of an E3 ubiquitin protein ligase27.Jun 6, 2015

How does HIF increase oxygen?

HIF activates genes involved in two vital processes. The first is angiogenesis, the formation of blood vessels. The second is the production of hemoglobin, oxygen-carrying red blood cells. Both assist in delivering more oxygen to the places that need it.Oct 14, 2019

What does HIF do to a cell?

HIF is a transcription factor that plays an essential role in the cellular response to low oxygen, orchestrating a metabolic switch that allows cells to survive in this environment. In immunity, infected and inflamed tissues are often hypoxic, and HIF helps immune cells adapt.Oct 6, 2020

What causes angiogenesis?

The mechanism of blood vessel formation by angiogenesis is initiated by the spontaneous dividing of tumor cells due to a mutation. Angiogenic stimulators are then released by the tumor cells. These then travel to already established, nearby blood vessels and activates their endothelial cell receptors.

Is HIF-1 an oncogene?

Collectively, our data show that HIF-1 is a pivotal pro-tumorigenic factor, controlling key oncogenic programs in both the epithelial tumor compartment and the tumor microenvironment.May 1, 2019

How does HIF regulate transcription?

Upon hypoxia, the HIF alpha subunits are stabilized and accumulate in the nucleus, where they dimerize with HIF1B, allowing them to bind to DNA and stimulate the transcription of their target genes.Oct 7, 2013

What is HIF 1bd?

Hypoxia-inducible factor 1 (HIF-1) is critically involved in cancer cell hypoxia adaptation, glycolysis, and angiogenesis. HIF-1 beta is associated with HIF-1 functions as a dimerization partner of HIF-1 alpha, and is on the other hand associated with carcinogenesis via dioxin signaling.Jul 28, 2014

What is the HIF1 protein?

HIF1 is a heterodimeric basic helix-loop-helix structure that is composed of HIF1A, the alpha subunit (this protein), and the aryl hydrocarbon receptor nuclear translocator ( Arnt ), the beta subunit. HIF1A contains a basic helix-loop-helix domain near the C-terminal, followed by two distinct PAS (PER-ARNT-SIM) domains, and a PAC (PAS-associated C-terminal) domain. The HIF1A polypeptide also contains a nuclear localization signal motif, two transactivating domains CTAD and NTAD, and an intervening inhibitory domain (ID) that can repress the transcriptional activities of CTAD and NTAD. There are a total of three HIF1A isoforms formed by alternative splicing, however isoform1 has been chosen as the canonical structure, and is the most extensively studied isoform in structure and function.

What is the role of HIF1A in cellular response?

The transcription factor HIF-1 plays an important role in cellular response to systemic oxygen levels in mammals. HIF1A activity is regulated by a host of post-translational modifications: hydroxylation, acetylation, and phosphorylation. HIF-1 is known to induce transcription of more than 60 genes, including VEGF and erythropoietin that are involved in biological processes such as angiogenesis and erythropoiesis, which assist in promoting and increasing oxygen delivery to hypoxic regions. HIF-1 also induces transcription of genes involved in cell proliferation and survival, as well as glucose and iron metabolism. In accordance with its dynamic biological role, HIF-1 responds to systemic oxygen levels by undergoing conformational changes, and associates with HRE regions of promoters of hypoxia-responsive genes to induce transcription.

What is the HIF1A gene?

HIF1A. Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 ( HIF-1) that is encoded by the HIF1A gene. The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF. HIF1A is a basic helix-loop-helix PAS domain containing protein, ...

Where is HIF1A found?

In hemangioblastoma, HIF1A expression is found in most cells sampled from the well-vascularized tumor. Although in both renal carcinoma and hemangioblastoma, the von Hippel-Lindau gene is inactivated, HIF1A is still expressed at high levels.

What is the Nobel Prize for Physiology?

The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF. HIF1A is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia.

Is HIF1A overexpressed in cancer?

HIF1A is overexpressed in many human cancers. HIF1A overexpression is heavily implicated in promoting tumor growth and metastasis through its role in initiating angiogenesis and regulating cellular metabolism to overcome hypoxia. Hypoxia promotes apoptosis in both normal and tumor cells. However, hypoxic conditions in tumor microenvironment especially, along with accumulation of genetic alternations often contribute to HIF1A overexpression.

Does p53 induce apoptosis?

Moreover, p53-independent pathway may also induce apoptosis through the Bcl-2 pathway. However, overexpression of HIF1A is cancer- and individual-specific, and depends on the accompanying genetic alternations and levels of pro- and anti-apoptotic factors present.

What is the role of HIF-1?

Hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix-PAS domain transcription factor, plays an integral role in the body's response to low oxygen concentrations, or hypoxia.

What is the target gene of HIF-1?

The target genes of HIF-1 encode proteins that increase O 2 delivery and mediate adaptive responses to O 2 deprivation. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, or various growth factors.

What is the role of HIF-1 in normoxia?

Under normoxia, HIF-1 alpha undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the subunit. In contrast, under hypoxic conditions, HIF-1 regulates the transcription of hundreds of genes in a cell type-specific manner.

What is the significance of alpha?

The level of significance of a hypothesis test is exactly equal to the probability of a Type I error. A Type I error consists of incorrectly rejecting the null hypothesis when the null hypothesis is actually true. The smaller the value of alpha, the less likely it is that we reject a true null hypothesis.

What is the level of significance of a hypothesis test?

This level of significance is a number that is typically denoted with the Greek letter alpha. One question that comes up in a statistics class is, “What value of alpha should be used for our hypothesis tests?”.

What happens if you get a false positive?

A false positive will result in anxiety for our patient but will lead to other tests that will determine that the verdict of our test was indeed incorrect. A false negative will give our patient the incorrect assumption that he does not have a disease when he in fact does.

What does it mean to have a level of significance?

This ends up being the standard by which we measure the calculated p-value of our test statistic. To say that a result is statistically significant at the level alpha just means that the p-value is less than alpha. For instance, for a value of alpha = 0.05, if the p-value is greater than 0.05, then we fail to reject the null hypothesis.

What is the HIF1A gene?

The aptly named HIF1A gene codes for the HIF-1a protein. There are two really well studied HIF1A genetic variants that generally increase the amount of HIF-1a that is available in cells. As you might imagine, this may increase the risk of cancer.

What is a transcription factor?

Basically, a transcription factor is like a switch that can turn on or off the transcription of genes. There are a couple of thousand different transcription factors in the human genome. HIF-1a (hypoxia-inducible factor-1 alpha) responds to the amount of oxygen available to the cell.

Why do cancer cells need oxygen?

Cancer cells grow rapidly and need a lot of oxygen. Thus, they need more blood vessels to bring in the O2 and they need nutrients. HIF-1a is often upregulated or increased in cancer and helps with the promotion of tumor growth by creating more blood vessels to bring in the oxygen.

Does Tamoxifen help with breast cancer?

Interestingly, tamoxifen, a treatment for estrogen-positive breast cancer, works in part by reducing HIF-1a levels. [ ref] Cytokines are inflammatory molecules that the body produces as part of the immune response. They are signals to increase inflammation.

Who is Debbie Moon?

Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information.

Does oxygen make ATP?

The use of oxygen normally occurs in the cellular process to make energy or ATP. (Yes, your cells have a backup route of anaerobic glycolysis which works without oxygen, but this isn’t as efficient for making ATP.) Thus, when oxygen levels drop, the HIF-1a levels rise, kicking off a bunch of processes.

What causes hypoxia in the body?

First, inflammation can cause hypoxia in a specific area of the body. For example, an inflamed joint due to arthritis will have a low supply of oxygen. Other conditions that cause hypoxia include heart disease, stroke, and kidney disease.

Structure

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Gene and Expression

Function

Regulation

Role in Cancer

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