S100 protein family (S100)

The S100 protein family consists of over 20 small, acidic proteins characterized by two EF-hand calcium-binding motifs (UniProt). These proteins function as both intracellular calcium sensors and extracellular signaling molecules, often referred to as damage-associated molecular patterns or DAMPs (PubMed, PMID: 26110551). Intracellularly, they regulate processes such as cell cycle progression, differentiation, and cytoskeleton organization by interacting with various effector proteins in a calcium-dependent manner. Extracellularly, S100 proteins like S100A8, S100A9, and S100B are secreted into the microenvironment where they bind to receptors such as the Receptor for Advanced Glycation End-products (RAGE) and Toll-like receptor 4 (TLR4), triggering pro-inflammatory and pro-survival pathways (PubMed, PMID: 30107173). Due to their overexpression in numerous pathologies, including various cancers, rheumatoid arthritis, and Alzheimer's disease, they are significant therapeutic targets and diagnostic biomarkers (StatPearls). Small molecule inhibitors and neutralizing antibodies are currently being developed to disrupt S100-mediated signaling, particularly in oncology and chronic inflammatory conditions.

Other names

CalgranulinS100 calcium-binding protein familyEF-hand calcium-binding proteinsS100 proteins

Inhibition of S100-protein interactions, blockade of extracellular S100 binding to receptors like RAGE or TLR4, and modulation of calcium-dependent signaling pathways (PubMed, PMID: 30107173).