hif-1 alpha levels may go up when____ course here

What is HIF-1?

Biology questions and answers. HIF-1α levels may go up when A Oxygen conditions are at normal physiologic levels. B Cells are experiencing hypoxic conditions. C Oxygen levels are high. D HIF-1α is bound to pVHL. E C and D. Question: HIF-1α levels may go up when A Oxygen conditions are at normal physiologic levels.

Is baseline HIF1 alpha level associated with high altitude pulmonary edema susceptibility?

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 …

How is hypoxia-inducible factor 1 alpha (HIF-1) activated by insulin?

With a clearer understanding of the HIF-1 pathway, efforts are directed at manipulation of this complex genetic process in order to ultimately increase or decrease cellular HIF-1 levels. Although a human transcription factor has yet to be successfully controlled through external manipulation, such a goal remains attractive as it may lead to non ...

What are the different types of HIF signaling pathways?

- Highest levels in kidney and heart - Overexpressed in majority of human cancers Under normoxic conditions, HIF-1 alpha is largely undetectable. Hypoxia needs to be induced in most cells and normal tissues. Location Cytoplasmic in normoxic conditions. Nuclear translocation in response to hypoxia. PMID: 9822602

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

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 genes does HIF activate?

HIF activates genes that control cellular oxygen homeostasis, including genes involved in oxygen consumption, erythrocyte production, angio- genesis, and mitochondrial metabolism. Hypoxic cells counter stress by transcriptional and post-transcriptional mechanisms, mainly regulated by HIF.

How does HIF regulate erythropoiesis?

Recent experimental evidence suggests that HIF promotes erythropoiesis through coordinated cell type-specific hypoxia responses, which include increased EPO production in the kidney and liver, enhanced iron uptake and utilization, as well as changes in the bone marrow microenvironment that facilitate erythroid ...

How do you test for HIF?

It is possible to measure HIF-1α in biological samples using an ELISA assay, although careful sample preparation and storage is essential. This may be of value in conditions in which tissue hypoxia may play a role, including cancer, cardiovascular disease and pulmonary disease.May 16, 2018

What does HIF 1 alpha do?

HIF-1alpha forms regulatory loop with YAP to coordinate hypoxia-induced adriamycin resistance in acute myeloid leukemia cells. EtaIotaF1alpha, EGR1 and SP1 co-regulate the erythropoietin receptor expression under hypoxia: an essential role in the growth of non-small cell lung cancer cells.

What result does C MYC have on transcription?

In cancer, c-myc is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer....Myc.MYC proto-oncogene, bHLH transcription factorIdentifiersNCBI gene4609HGNC7553OMIM1900808 more rows

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

What regulates HIF?

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 regulate erythropoiesis in normoxic conditions?

Recent experimental evidence suggests that HIF promotes erythropoiesis through coordinated cell type-specific hypoxia responses, which include increased EPO production in the kidney and liver, enhanced iron uptake and utilization, as well as changes in the bone marrow microenvironment that facilitate erythroid ...

Is HIF part of the oxygen cascade?

The HIF signaling cascade mediates the effects of hypoxia, the state of low oxygen concentration, on the cell.

When is EPO released?

The hormone tells stem cells in the bone marrow to make more red blood cells. EPO is made by cells in the kidney. These cells release more EPO when blood oxygen level is low.Jul 11, 2019

What is the meaning of HIF?

HIFAcronymDefinitionHIFHousing Inspection FoundationHIFHeavy Ion FusionHIFHosei International Fund (Hoei University; Japan)HIFHost Interface7 more rows

Who discovered HIF?

2. Discovery of the HIF-1 protein. HIF-1 was initially discovered by Semenza and co-workers15 in 1991 during a study conducted on erythropoietin (EPO) gene, a gene responsible for encoding erythropoietin hormone for red blood cells production.

What is the hypoxia response element?

HIF recognizes hypoxia response elements (HREs), a TFB within the promoters of a large number of genes, and binds to it after hypoxic induction and enhances the expression of the gene (Wenger et al., 2005).Jul 16, 2019

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 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 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, ...

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 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 role of HIF-1 alpha?

HIF-1 alpha, a protein rapidly responsive to all-trans retinoic acid, plays a role in all-trans retinoic acid-induced differentiation of leukemic cells. The role of hypoxia inducible factor-1 on the expression of cystic fibrosis transmembrane conductance regulator and chloride and water flux in intestinal cells is reported.

What is ANGPTL4?

ANGPTL4 is a target gene of HIF-1alpha and acts as an important regulator in the metastasis of hepatocellular carcinoma. findings show that monocyte-derived dendritic cells, exposed to hypoxia, expressed high levels of the hypoxia-inducible factor (HIF)-1alpha, associated with upregulation of BNIP3 and BAX expression.

Does HIF-1 inhibit tumor growth?

HIF-1alpha, HIF-2alpha, or both HIF-1alpha and HIF-2alpha genes directly inhibited tumor cell proliferation. elevated expression of the hypoxia-inducible transcription factor-1 (HIF-1) and HIF-2 is a key feature of many human cancers and has been shown to promote cellular processes, which facilitate tumor progression.

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.

Overview

Structure

Gene and expression

Function

Regulation

Role in cancer

Interactions

See also