| S100B belongs to the S100 family of EF-hand calcium-binding proteins and serves primarily as an intracellular regulator and extracellular signaling molecule abundant in astrocytes and oligodendrocytes of the central nervous system. It consists of two EF-hand motifs per monomer that form antiparallel homodimers upon calcium binding, enabling interaction with diverse targets through conformational changes that expose hydrophobic surfaces. S100B modulates cytoskeletal dynamics by binding F-actin and microtubule-associated proteins, promoting stress fiber disassembly and membrane ruffling via inhibition of PKC phosphorylation, while also influencing energy metabolism and Ca2+ homeostasis to regulate astrocyte proliferation, differentiation, and migration. S100B acts in a dose-dependent manner through RAGE receptor ligation, triggering at low physiological levels Ras/MEK/ERK/NF-κB/Bcl-2 signaling for neuroprotection, neurite outgrowth, and astrocyte proliferation, but at high pathological concentrations hyperactivating ERK with ROS overproduction to induce neuronal apoptosis; this biphasic action extends to RAGE/p38MAPK/pAkt/mTOR/HIF1α pathways that upregulate VEGF and NO while suppressing p53 in cancer cells. S100B maintains glial shape and motility critical for blood-brain barrier integrity and synaptic support, positioning it as a key target for studying astrocyte-oligodendrocyte interactions in development and repair where calcium flux dictates cellular responses. Its expression in gray matter protoplasmic astrocytes and white matter oligodendrocytes supports tissue-specific roles in myelination and neuroinflammation modulation. Dysregulation with chronic elevation promotes tumor angiogenesis and invasion in colorectal cancer via proinflammatory NF-κB activation. |
Lane 1: SK-MEL-28
