Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target

Heat shock protein 27 (HSP27) belongs to the small molecular weight heat shock protein (HSP) family (12–43 kDa). HSP27 and other members of the small HSP family share a conserved c-terminal domain, the α-crystallin domain, which is identical to the vertebrate eye lens α-crystallin [1]. HSP27 was initially characterized in response to heat shock [2] as a protein chaperone that facilitates the proper refolding of damaged proteins [3,4]. Continued investigation of HSP27 revealed that the protein responds to cellular stress conditions other than heat shock; for example oxidative stress and chemical stress. During oxidative stress, HSP27 functions as an antioxidant, lowering the levels of reactive oxygen species (ROS) by raising levels of intracellular glutathione and lowering the levels of intracellular iron [5,6]. The protein functions as an anti-apoptotic agent under conditions of chemical stress by interacting with both mitochondrial dependent and independent pathways of apoptosis (Figure？1). HSP27 binds DAXX during Fas-FasL mediated apoptosis and prevents the subsequent binding of Ask1 by DAXX [7]. HSP27 also interacts with Bax and cytochrome c, thereby preventing mitochondrial dependent apoptosis [8,9]. HSP27 is particularly involved in protection from programmed cell death by inhibition of caspase-dependent apoptosis [10]. These anti-apoptotic properties in response to chemicals (perceived as stress by cells) has had major ramifications on the success of certain chemotherapies such as doxorubicin and gemcitabine [11,12]. Lastly, HSP27 has been characterized with the ability to regulate actin cytoskeletal dynamics during heat shock and other stress conditions, functioning both to promote actin polymerization and as an actin capping protein [13-15].HSP27 is present at basal levels in cells and tissues, and is organized as large oligomers [16]. The protein is phosphorylated by MAPKAP kinase 2/3 via the activation of the P38 MAPK pathway [14] at multiple serine residu