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 Experiment Videos

Nucleocytoplasmic functionality of metallothionein

E S Woo1, J S Lazo

  • 1Department of Pharmacology, University of Pittsburgh, School of Medicine, Pennsylvania 15261, USA.

Cancer Research
|October 23, 1997
PubMed
Summary

Metallothioneins (MTs) protect cells from toxins. Their location matters: cytoplasmic MTs reduce oxidative stress and heavy metal damage, while nuclear MTs combat mutagenic agents.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Metastasis-associated phosphatase PRL-2 regulates tumor cell migration and invasion.

Oncogene·2011
Same author

Astrogliosis and behavioral changes in mice lacking the neutral cysteine protease bleomycin hydrolase.

Neuroscience·2007
Same author

Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25.

Journal of medicinal chemistry·2001
Same author

Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs.

Cancer research·2001
Same author

New inhibitors of the thioredoxin-thioredoxin reductase system based on a naphthoquinone spiroketal natural product lead.

Bioorganic & medicinal chemistry letters·2001
Same author

Small molecule inhibitors of dual specificity protein phosphatases.

Oncogene·2001

Area of Science:

  • Cell Biology
  • Biochemistry
  • Toxicology

Background:

  • Nucleocytoplasmic partitioning of proteins is crucial for cellular function.
  • Metallothioneins (MTs) are small, stress-inducible proteins with protective roles against oxidants, mutagens, and anticancer drugs.
  • MTs exhibit distinct subcellular localization patterns despite their small molecular weight.

Purpose of the Study:

  • To investigate the subcellular location-specific functionality of Metallothioneins (MTs).
  • To determine if nuclear or cytoplasmic expression of MTs confers differential protection against specific cellular insults.
  • To elucidate the role of nucleocytoplasmic partitioning in the protective mechanisms of small proteins.

Main Methods:

  • Utilized a regulated expression system to restrict MT expression to either the nucleus or cytoplasm in MT-null fibroblasts.
  • Assessed the impact of subcellularly localized MTs on intracellular reactive oxygen species (ROS) levels.
  • Evaluated the cytoprotective effects of MTs against tert-butyl hydroperoxide (oxidant), CdCl2 (heavy metal), and N-methyl-N'-nitro-N-nitrosoguanidine (mutagen).

Main Results:

  • Cytoplasmic MT expression significantly decreased intracellular ROS levels and provided greater cytoprotection against tert-butyl hydroperoxide compared to nuclear expression.
  • Cytoplasmic MT expression protected against CdCl2 cytotoxicity, whereas nuclear MT expression conferred protection against the mutagen N-methyl-N'-nitro-N-nitrosoguanidine.
  • Demonstrated differential functional outcomes based on the subcellular localization of MTs.

Conclusions:

  • Essential cytotoxic targets for oxidants and heavy metals are primarily located in the cytoplasm.
  • Nucleocytoplasmic partitioning is critical for the functional efficacy of small protective proteins like MTs.
  • Subcellular localization dictates the specific protective roles of MTs against different types of cellular damage.

Related Experiment Videos