S100 calcium-binding protein (S100)

The S100 protein family consists of low-molecular-weight calcium-binding proteins characterized by two EF-hand calcium-binding motifs (Donato et al., 2013, Physiological Reviews). These proteins are primarily found in vertebrates and function as key regulators of diverse cellular processes, including cell cycle progression, differentiation, and motility, by acting as calcium sensors that modulate the activity of various effector proteins (UniProt). In many diseases, S100 proteins are dysregulated; for instance, S100B is a well-known marker for melanoma and brain injury, while S100A8 and S100A9 (calprotectin) are critical mediators of the inflammatory response (Bresnick et al., 2015, Nature Reviews Cancer). From a therapeutic perspective, S100 proteins are targeted to disrupt their interaction with receptors like RAGE or intracellular partners like p53, which are implicated in tumor progression and chronic inflammation (Heizmann et al., 2002, Methods in Molecular Biology). Several small molecules, such as tasquinimod and paquinimod, have been developed to target specific S100 members to treat autoimmune conditions and certain cancers (PubMed). Their utility as both diagnostic biomarkers and therapeutic targets makes them a significant focus in clinical oncology and neurology.

Other names

S-100S100 protein familyEF-hand calcium-binding proteinS100 calcium binding protein

Inhibition of protein-protein interactions (PPIs) between S100 proteins and their ligands, such as the Receptor for Advanced Glycation End-products (RAGE), p53, or TLR4, thereby modulating downstream signaling pathways involved in inflammation, cell survival, and tumor progression (Donato et al., 2013, Physiological Reviews).