Homology of HSP16.2 to αB-crystallin, the induction of its synthesis to heat stress and its ATP-independent chaperone activity suggested that HSP16.2 is a novel small Heat Shock Protein. Suppression of HSP16.2 sensitized cells to apoptotic stimuli, while the over-expressing of HSP16.2 protected cells against H2O2 and taxol-induced cell death. Under stress conditions, HSP16.2 inhibited the release of cytochrome c from the mitochondria, nuclear translocation of AIF and endonuclease G, and caspase-3 activation by protecting the integrity of the mitochondrial membrane system. It was demonstrated that HSP16.2 interacts with HSP90, and that the presence of functionally active HSP90 is a prerequisite of the cytoprotective action of HSP16.2. HSP16.2 also facilitated lipid rafts formation, which could serves as scaffolds for the activation of Akt. The inhibition of PI-3-kinase-Akt pathway by LY-294002, or wortmannin, significantly decreased the cytoprotective effect of HSP16.2. These data indicate that one of the main mechanisms by which HSP16.2 inhibits apoptosis is through its interaction with functionally active HSP90, promoting lipid raft formation and the activation of PI-3-kinase-Akt cytoprotective pathway. Expression of HSP16.2 varies in different types of brain tumors and a positive correlation can be found between the tumor grade and the quantity of HSP16.2 in the tumor cells' cytoplasm. Thus, HSP16.2 may become a valuable marker for brain cancer diagnosis, or a possible target of cancer therapy.
|Title of host publication||Small Stress Proteins and Human Diseases|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||7|
|Publication status||Published - Dec 1 2011|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)