Mortalin-Bcl-2 Interaction Acts as a Tumor Suppressor Mechanism in Cancer Cells

摘要

The cellular apoptosis is controlled by Bcl-2 family of proteins consisting of both pro-apoptotic and antiapoptotic members,predominantly residing in mitochondria.Their key function is to control the release of apoptotic factors from mitochondria to cytosol.They also preserve mitochondrial integrity and prevent loss of mitochondrial membrane potential and cell death.Mortalin/mthsp70/PBP74/GRP75,a member of the heat shock protein 70 (hsp70) family,is also predominantly present in mitochondria and is involved in mitochondrial import,control of membrane permeability and reactive oxygen species (ROS) production.Mortalin was shown to interact with p53 causing its cytoplasmic sequestration and hence inactivation of its tumor suppressor function.Here we report that mortalin and Bcl-2 interact with each other and these interactions cause release of p53 from mortalin-p53 complexes.Although both mortalin and Bcl-2 are upregulated in cancer cells and are shown to have anti-apoptotic function,our study suggests that these anti-apoptotic proteins interact and bring in the tumor suppression at the same time.The data (i) provide evidence of the existence of tumor suppression mechanism even in cancer cells and by the proteins that have anti-apoptotic impact and (ii) endorse the complexity and multidirectional regulation of the proliferation capacity of cancer cells.