The HSPD1 gene encodes a protein known as HSP60 or Hsp60, also commonly referred to as Cpn60. This protein is a molecular chaperone typically localized inside mitochondria where it forms a chaperoning machine with HSP10 (encoded by the HSPE1 gene), also called Cpn10, to assist protein folding inside the organelle. Hsp60 also occurs in the cytosol, plasma-cell membrane, intercellular space, and blood. Its functions in all these extramitochondrial locations are poorly understood. While the canonical functions of Hsp60 are considered to be cytoprotective, anti-stress and maintenance of protein homeostasis, other roles are currently being investigated. For example, Hsp60 participates in the pathogenesis of diseases in various ways in certain types of cancer, and chronic inflammatory and autoimmune pathological conditions. These are considered chaperonopathies by mistake, in which a normal chaperone (normal at least as far as it can be determined by current methods to study the structure of a molecule available only at extremely low concentrations and quantities) turns against the organism instead of protecting it, favouring the growth and dissemination of cancer cells, or the initiation-progression of inflammation, for instance. In addition, Hsp60 mutations cause at least two types of severe genetic chaperonopathies. All this knowledge is expanding nowadays clearly pointing to Hsp60 as a potential target for chaperonotherapy by replacement when it is defective or by inhibition when it is pathogenic....

Human Major Histocompatibility Complex (MHC) Class I Chain-Related gene A (MICA) is located 46 Kb centromeric to the HLA-B locus on the short arm of human chromosome 6 and encodes for a 62-kda cell surface glycoprotein. It is expressed on endothelial cells, dendritic cells, fibroblasts, epithelial cells, and many tumours and serves as target for both cellular and humoral immune responses in transformed cells. MICA protein at normal states has a low level of expression in epithelial tissues but is upregulated in response to various stimuli of cellular stress. MICA also functions as a ligand recognized by the activating receptor NKG2D that is expressed on the surface of NK, NKT, CD8+ and TCRγδ+ T cells. Allelic variants of MICA due to a single amino acid substitution at position 129 in the α2 domain have been reported to result in large differences in NKG2D binding. These variable affinities have been suggested to affect thresholds of NK cell triggering and T cell modulation in autoimmune diseases and malignancies. MICA molecules exist also in soluble forms (sMICA) and altered serum levels of sMICA have been reported in multiple states of health and disease....

The BIRC6 gene (BRUCE/APOLLON) encodes the cytoplasmic protein BIRC6 in mammals, consisting of a single N-terminal baculoviral IAP repeat (BIR) domain and a C-terminal ubiquitin-conjugating (UBC) domain. Of the huge protein size at 528 kDa, BIRC6 demonstrated pleiotropic functions including inhibition of apoptosis, cytoprotection, regulation of cytokinesis, mitosis, autophagy and neutrophil differentiation. With the BIR domain, BIRC6 is defined as a member of the Inhibitor of Apoptosis (IAP) family. Through its BIR domain, BIRC6 binds to active caspases, including caspases-3, 6, 7 and 9 and accounts for its ability to inhibit the caspase cascade and ultimately apoptosis. The UBC domain has chimeric E2/E3 ubiquitin ligase activity where it facilitates proteosomal degradation of various proteins, including pro-apoptotic proteins p53, caspases, Smac and mitotic regulator cyclin A. More importantly, the UBC domain plays an indispensable role in embryonic development in mammals and spermatogenesis in Drosophila. Increasing evidence supports the cancer promoting role of BIRC6. Elevated BIRC6 expression has been found in a variety of cancers and was shown to contribute to treatment resistance....

The CEACAM5 gene encodes carcinoembryonic antigen (CEA), which was first identified as an oncofetal antigen in 1965 in human colon cancer tissue extracts. CEA is a heavily glycosylated protein that belongs to the CEA-related cell adhesion molecule (CEACAM) family of the immunoglobulin (Ig) gene superfamily. CEA is closely related to CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, and CEACAM8. CEA is also expressed at low levels in normal tissues of epithelial origin in a polarized manner and found only at the luminal portion of the cell, but not at the basolateral surface. CEA in normal tissues is now considered to protect the luminal organs of the body from microbial infection by binding and trapping infectious microorganisms. In contrast, the expression of CEA is frequently high in various carcinomas. Cancer cells not only lose polarized expression of CEA, but also actively cleave CEA from their surface by phospholipases, resulting in increased serum concentrations of CEA. The serum CEA levels may be monitored to detect a response to cancer therapy or disease recurrence and serve as a prognostic indicator in patients with various cancers, where elevated levels indicate a poor prognosis and correlate with a reduced overall survival. Cell-bound CEA has served as a target for tumor imaging and various cancer therapies....

ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary))...