Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
S100 proteins regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription and differentiation. Twenty members have been identified so far, and altogether, S100 proteins represent the largest subgroup in the EF-hand Ca2+ -binding protein family. A unique feature of these proteins is that individual members are localized in specific cellular compartments from which some are able to relocate upon Ca2+ activation, transducing the Ca2+ signal in a temporal and spacial manner by interacting with different targets specific for each S100 protein. Some members are even secreted from cells exerting extracellular, cytokine-like activities partially via the surface receptor RAGE (receptor for advanced glycation endproducts) with paracrine effects e.g. on neurons, promoting their survival during development or after injury.
Another important aspect is that 14 bona fide S100 genes are found in a gene cluster on human chromosome 1q21 where a number of chromosomal abnormalities occur. This results in a deregulated expression of some S100 genes associated with neoplasias. Recently, S100 proteins have received increasing attention due to their close association with several human diseases including cardiomyopathy, neurodegenerative disorders and cancer. They have also been proven to be valuable in the diagnostic of these diseases, as predictive markers of improving clinical management, outcome and survival of patients and are considered having a potential as drug targets to improve therapies.