Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis
Takehiko Dohi, … , Janet Plescia, Dario C. Altieri
Takehiko Dohi, … , Janet Plescia, Dario C. Altieri
Published October 15, 2004
Citation Information: J Clin Invest. 2004;114(8):1117-1127. https://doi.org/10.1172/JCI22222.
View: Text | PDF
Article Oncology

Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis

  • Text
  • PDF
Abstract

Evasion of apoptosis is a hallmark of cancer, but the molecular circuitries of this process are not understood. Here we show that survivin, a member of the inhibitor of apoptosis gene family that is overexpressed in cancer, exists in a novel mitochondrial pool in tumor cells. In response to cell death stimulation, mitochondrial survivin is rapidly discharged in the cytosol, where it prevents caspase activation and inhibits apoptosis. Selective targeting of survivin to mitochondria enhances colony formation in soft agar, accelerates tumor growth in immunocompromised animals, and abolishes tumor cell apoptosis in vivo. Therefore, mitochondrial survivin orchestrates a novel pathway of apoptosis inhibition, which contributes to tumor progression.

Authors

Takehiko Dohi, Elena Beltrami, Nathan R. Wall, Janet Plescia, Dario C. Altieri

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Mitochondrial localization of survivin. (A) Survivin localization in tum...
Mitochondrial localization of survivin. (A) Survivin localization in tumor cell lines. Cytosolic (left panel) or mitochondrial (right panel) extracts from the indicated tumor cell lines were analyzed by immunoblotting. MW, molecular weight. (B) Subcellular fractionation of normal tissues. Mitochondrial (M) or cytosolic (C) fractions extracted from normal testis, spleen, and liver or unfractionated HeLa cell extracts were analyzed by immunoblotting. Cox-4 was used as a mitochondrial marker. (C–E) Immunoelectron microscopy. Mitochondrial pellets (C and E) isolated from MCF-7 cells or whole MCF-7 cell extracts (D) were stained with nonimmune IgG (C) or an antibody to survivin (D) followed by colloidal gold-conjugated secondary IgG. Isolated mitochondrial pellets (E) were simultaneously stained with antibodies to survivin (12 nm diameter gold particles) and Smac (6 nm diameter gold particles). Magnification, ×53,000 (C and D), ×104,000 (E).
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts