Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Leaky Scanning02:28

Leaky Scanning

4.5K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
4.5K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

6.3K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
6.3K
Experimental RNAi02:15

Experimental RNAi

6.5K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.1K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Gene Therapy00:59

Gene Therapy

22.1K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
22.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Inhibition of KDEL Receptors Remodels the Tumor Microenvironment for T Cell Independent Tumor Regression.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same author

A PML1-CCL5-PI3K/MAPK feedback loop governs survival of endocrine-resistant breast cancer cells.

Cell death and differentiation·2026
Same author

Gut microbe-derived <i>N</i>-acyl serinol lipids shape host postprandial metabolic homeostasis.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

A blood-based transcriptomic signature stratifies severe Crohn's disease and defines potentially targetable therapeutic pathways.

Frontiers in gastroenterology (Lausanne, Switzerland)·2026
Same author

Gene expression profiling identifies potential biomarkers for vaso-occlusive episodes in sickle cell disease.

JCI insight·2026
Same author

dCas9 Targeted Proteome Profiling Reveals p300-Mediated Reciprocal Regulation of SMAD and SP1 as a Driver of GM2-synthase Transcription in Renal Cell Carcinoma.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology·2026

Related Experiment Video

Updated: Apr 27, 2026

Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
09:01

Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles

Published on: September 27, 2013

10.5K

Programmed translational readthrough generates antiangiogenic VEGF-Ax.

Sandeepa M Eswarappa1, Alka A Potdar2, William J Koch1

  • 1Department of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Cell
|June 21, 2014
PubMed
Summary

Mammalian cells utilize programmed translational readthrough (PTR) to create novel VEGF-Ax protein isoforms from vascular endothelial growth factor A (VEGFA) mRNA. This newly discovered mechanism reveals a unique antiangiogenic factor with significant implications in human tissues and disease.

More Related Videos

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

6.8K
Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
07:48

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia

Published on: June 8, 2019

8.2K

Related Experiment Videos

Last Updated: Apr 27, 2026

Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
09:01

Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles

Published on: September 27, 2013

10.5K
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

6.8K
Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
07:48

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia

Published on: June 8, 2019

8.2K

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Translational readthrough expands proteomes in simpler organisms by extending translation past stop codons.
  • Vascular Endothelial Growth Factor A (VEGF-A) is a key regulator of angiogenesis.

Purpose of the Study:

  • To investigate programmed translational readthrough (PTR) in mammalian cells.
  • To identify novel protein isoforms generated by PTR and their functions.

Main Methods:

  • Analysis of VEGFA mRNA 3' UTR cis-acting elements.
  • Identification of RNA-binding proteins involved in PTR using hnRNP A2/B1.
  • Functional assays for VEGF-Ax antiangiogenic activity.
  • Genome-wide analysis for additional readthrough targets.

Main Results:

  • Discovered programmed translational readthrough (PTR) in mammalian endothelial cells, generating VEGF-Ax from VEGFA mRNA.
  • Identified a cis-acting element in the VEGFA 3' UTR and hnRNP A2/B1 as crucial for directing serine decoding of the UGA stop codon.
  • VEGF-Ax exhibits antiangiogenic properties, contrasting with VEGF-A's proangiogenic role.
  • VEGF-Ax is expressed in human tissues but depleted in colon adenocarcinoma; AGO1 and MTCH2 identified as other readthrough targets.

Conclusions:

  • Revealed a novel protein-regulated PTR mechanism in vertebrates.
  • VEGF-Ax represents a new antiangiogenic factor with potential roles in human health and disease.
  • Identified new targets and regulators of translational readthrough in mammalian systems.