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

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

9.8K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

4.1K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

8.7K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.7K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

6.2K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.2K
Leaky Scanning02:28

Leaky Scanning

5.4K
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...
5.4K
Protein Networks02:26

Protein Networks

4.3K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.3K

You might also read

Related Articles

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

Sort by
Same author

CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.

Cancer discovery·2026
Same author

Heterogeneity in endpoints, monitoring methods and blanking periods in clinical trials of atrial fibrillation ablation: a systematic review and meta-analysis.

Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing·2026
Same author

Late Fracture of Stylet-driven Lead Intended for Conduction System Pacing 2 Years After Implant.

The Journal of innovations in cardiac rhythm management·2026
Same author

Author Correction: Community benchmarking and evaluation of human unannotated microprotein detection by mass spectrometry based proteomics.

Nature communications·2026
Same author

P-glycoprotein-mediated efflux of rapaprotin-L dictates sensitivity of cancer cells to the inducer of 26S proteasome disassembly.

European journal of pharmacology·2026
Same author

Author Correction: Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors.

Nature communications·2026

Related Experiment Video

Updated: Nov 19, 2025

An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

3.8K

Noncanonical open reading frames encode functional proteins essential for cancer cell survival.

John R Prensner1,2,3, Oana M Enache1, Victor Luria4

  • 1Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Nature Biotechnology
|January 29, 2021
PubMed
Summary

Many noncanonical open reading frames (ORFs) encode biologically active proteins, with some showing essentiality in cancer cell lines. One such protein, GREP1, is a potential therapeutic target in breast cancer.

More Related Videos

Mass Spectrometry-Based Proteomics Analyses Using the OpenProt Database to Unveil Novel Proteins Translated from Non-Canonical Open Reading Frames
07:38

Mass Spectrometry-Based Proteomics Analyses Using the OpenProt Database to Unveil Novel Proteins Translated from Non-Canonical Open Reading Frames

Published on: April 11, 2019

13.1K
De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
08:23

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Published on: February 18, 2022

3.9K

Related Experiment Videos

Last Updated: Nov 19, 2025

An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

3.8K
Mass Spectrometry-Based Proteomics Analyses Using the OpenProt Database to Unveil Novel Proteins Translated from Non-Canonical Open Reading Frames
07:38

Mass Spectrometry-Based Proteomics Analyses Using the OpenProt Database to Unveil Novel Proteins Translated from Non-Canonical Open Reading Frames

Published on: April 11, 2019

13.1K
De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
08:23

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Published on: February 18, 2022

3.9K

Area of Science:

  • Genomics
  • Proteomics
  • Cancer Biology

Background:

  • Genomic analyses predict numerous noncanonical open reading frames (ORFs) in the human genome, but their functional relevance remains largely unexplored.
  • Experimental interrogation of 553 candidate noncanonical ORFs was performed to assess their biological activity and protein-coding potential.

Discussion:

  • 57 noncanonical ORFs induced viability defects upon knockout in human cancer cell lines, suggesting essential functions.
  • Evidence of protein expression was observed for 257 candidates, and 401 induced gene expression changes, indicating active biological roles.
  • Clustered regularly interspaced short palindromic repeat (CRISPR) tiling and start codon mutagenesis confirmed that observed effects were translation-dependent, not RNA-mediated.

Key Insights:

  • The noncanonical ORF G029442, renamed glycine-rich extracellular protein-1 (GREP1), encodes a secreted protein highly expressed in breast cancer.
  • GREP1 knockout demonstrated preferential essentiality in breast cancer-derived cell lines, highlighting its specific role in this cancer type.
  • GREP1 expression correlates with increased levels of the oncogenic cytokine GDF15, which can rescue growth inhibition caused by GREP1 knockout.

Outlook:

  • Noncanonical ORFs represent a significant source of novel, biologically active proteins with potential therapeutic applications.
  • GREP1 and its associated pathway involving GDF15 present a promising avenue for targeted breast cancer therapies.
  • Further research into noncanonical ORFs could uncover new drug targets and therapeutic strategies across various cancers.