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.

Keywords::

• apoptosis
• fibroblast
• MVP
• senescence
• survival