Targeting major vault protein in senescence-associated apoptosis resistance.

Abstract

BACKGROUND:

Recent studies have shown that major vault protein (MVP) is involved in intracellular signaling, cell survival, differentiation and innate immunity and that it is not directly responsible for nucleo-cytoplasmic drug transport in multi-drug-resistant cancer cell lines. Recently, we reported that MVP increases with age both in vitro and in vivo, and that age-related upregulation of MVP facilitates apoptosis resistance of senescent human diploid fibroblasts (HDFs) based on the interaction with c-Jun-mediated downregulation of bcl-2.

OBJECTIVES:

To discuss the role of MVP in cell survival and signaling in the development of resistance to apoptosis exhibited by senescent HDFs.

CONCLUSIONS:

MVP represents a versatile platform for regulation of cellular signaling and survival and is a potential therapeutic target for modulation of resistance to apoptosis, implicated in aging modulation and cancer treatment.

• Authors: Sung Jin Ryu, Sang Chul Park
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 13 Issue 4 Pg. 479-84 (Apr 2009) ISSN: 1744-7631 [Electronic] England
• PMID: 19335069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Neoplasm Proteins
• Vault Ribonucleoprotein Particles
• major vault protein

Topics

• Aging (metabolism)
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects, physiology)
• Cell Survival (physiology)
• Cellular Senescence
• Drug Delivery Systems
• Drug Design
• Drug Resistance, Multiple (physiology)
• Fibroblasts (pathology)
• Gene Expression Regulation, Neoplastic
• Genes, bcl-2
• Genes, jun
• Humans
• Mice
• Neoplasm Proteins (antagonists & inhibitors, physiology)
• Signal Transduction (physiology)
• Vault Ribonucleoprotein Particles (antagonists & inhibitors, deficiency, physiology)