title: Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications.
abstract: Heat shock proteins (HSPs) of eukaryotes are evolutionarily conserved molecules present in all the major intracellular organelles. They mainly function as molecular chaperones and participate in maintenance of protein homeostasis in physiological state and under stressful conditions. Despite their relative abundance, the large HSPs, i.e., Hsp110 and glucose-regulated protein 170 (Grp170), have received less attention compared to other conventional HSPs. These proteins are distantly related to the Hsp70 and belong to Hsp70 superfamily. Increased sizes of Hsp110 and Grp170, due to the presence of a loop structure, result in their exceptional capability in binding to polypeptide substrates or non-protein ligands, such as pathogen-associated molecules. These interactions that occur in the extracellular environment during tissue injury or microbial infection may lead to amplification of an immune response engaging both innate and adaptive immune components. Here, we review the current advances in understanding these large HSPs as molecular chaperones in proteostasis control and immune modulation as well as their therapeutic implications in treatment of cancer and neurodegeneration. Given their unique immunoregulatory activities, we also discuss the emerging evidence of their potential involvement in inflammatory and immune-related diseases.
authors.affiliation: Department of Immunology, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Daming
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Department of Cellular Stress Biology, Roswell Park Cancer Institute , Buffalo, NY , USA.
authors.forename: John
authors.initials: J
authors.lastname: Subjeck
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA; VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
keywords: antigen cross-presentation; cytoprotection; glucose-regulated protein 170; heat shock protein 110; inflammatory disease; innate immunity