Homocitrullinated heat shock protein 60 (Homocit-HSP60)

Homocitrullinated heat shock protein 60 (HSP60) is a post-translationally modified form of the mitochondrial chaperonin HSP60, where lysine residues are converted to homocitrulline through a process known as carbamylation [15, 18]. This modification typically occurs under conditions of cellular stress, chronic inflammation, or renal failure, often driven by the reaction of cyanate (derived from urea or myeloperoxidase activity) with protein amino groups [15, 18]. In the context of oncology, homocitrullinated HSP60 serves as a stress-induced post-translational modification (siPTM) neoantigen that is selectively expressed by cancer cells undergoing autophagy or metabolic stress [3, 12]. This unique expression profile makes homocitrullinated HSP60 a promising therapeutic target for cancer vaccines, such as Scancell's Modi-2, which is designed to induce potent CD4+ cytotoxic T-cell responses against tumor cells while sparing healthy tissues [20, 23]. Beyond its role in cancer, homocitrullinated HSP60 is a significant autoantigen in autoimmune disorders like rheumatoid arthritis, where it is recognized by anti-carbamylated protein (anti-CarP) antibodies [10, 15]. These antibodies are associated with increased joint damage and chronic inflammation, highlighting the protein's dual role as both a pathological autoantigen and a potential therapeutic target for immunotherapy [10, 13].

Other names

Carbamylated heat shock protein 60Carbamylated HSP60Homocit-HSP60HSPD1 (homocitrullinated form)Chaperonin 60 (homocitrullinated form)

Induction of CD4+ cytotoxic T-cell responses against stress-induced post-translational modification (siPTM) neoantigens