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

Master Transcription Regulators02:23

Master Transcription Regulators

8.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K
Abnormal Proliferation02:23

Abnormal Proliferation

5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

38.8K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

9.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

3.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

12.1K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
12.1K

You might also read

Related Articles

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

Sort by
Same author

MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth.

Signal transduction and targeted therapy·2026
Same author

Overexpression of ONECUT1 suppresses hepatoblastoma progression via modulating tumor cell growth and tumor microenvironment.

Cell & bioscience·2026
Same author

The Novel HSF1 Inhibitor NXP800 Exhibits Robust Antitumor Activity in Hepatocellular Carcinoma.

International journal of molecular sciences·2026
Same author

Distinct molecular pathways regulated by activated AKT and YAP signaling during intrahepatic cholangiocarcinoma progression.

Journal of hepatology·2026
Same author

Targeting Fatty Acids in Liver Cancer: Molecular Insights and Drug Approaches.

Biomolecules·2026
Same author

Supplementary biomarker testing in molecular tumor boards increases actionable therapy recommendations: a prospective real-world study of 658 patients.

BMC medicine·2026

Related Experiment Video

Updated: Mar 23, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

61.6K

NORE1A Regulates MDM2 Via β-TrCP.

M Lee Schmidt1, Diego F Calvisi2, Geoffrey J Clark3

  • 1Department of Pharmacology and Toxicology, James Graham Brown Cancer Center Molecular Targets Group, University of Louisville, Louisville, KY 40202, USA. lee.schmidt@louisville.edu.

Cancers
|March 30, 2016
PubMed
Summary

Novel Ras Effector 1A (NORE1A) targets Mouse Double Minute 2 Homolog (MDM2) for degradation, impacting tumor suppressor p53 levels. Loss of NORE1A promotes MDM2 expression, with implications for cancer biology.

Keywords:
MDM2NORE1ARasβ-TrCP

More Related Videos

Inducible and Reversible Dominant-negative DN Protein Inhibition
08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.8K
Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
09:15

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC

Published on: May 9, 2020

5.9K

Related Experiment Videos

Last Updated: Mar 23, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

61.6K
Inducible and Reversible Dominant-negative DN Protein Inhibition
08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.8K
Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
09:15

Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC

Published on: May 9, 2020

5.9K

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • Mouse Double Minute 2 Homolog (MDM2) is an oncogenic negative regulator of the tumor suppressor p53.
  • MDM2 targets p53 for proteasomal degradation via its ubiquitin ligase activity.
  • MDM2 overexpression is common in human cancers, indicating its role in tumorigenesis.

Purpose of the Study:

  • To investigate the regulatory role of RASSF5/NORE1A in MDM2 protein levels.
  • To elucidate the mechanism by which NORE1A influences MDM2 ubiquitination and degradation.
  • To understand the functional consequences of the NORE1A-MDM2 interaction on p53 regulation and cellular phenotypes.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Western blotting to assess protein levels and ubiquitination.
  • Overexpression and knockdown studies to evaluate functional effects.

Main Results:

  • RASSF5/NORE1A directly interacts with the SCF-β-TrCP ubiquitin ligase complex.
  • NORE1A promotes MDM2 ubiquitination and subsequent degradation through SCF-β-TrCP.
  • Suppression of NORE1A leads to increased MDM2 protein levels.
  • MDM2 antagonizes the senescence-inducing effects of NORE1A overexpression.

Conclusions:

  • NORE1A acts as a negative regulator of MDM2 protein stability.
  • This mechanism provides a novel pathway for Ras/NORE1A to modulate p53 levels.
  • Dysregulation of this pathway, particularly loss of NORE1A expression in tumors, has significant implications for cancer development and progression.