Fucosylated chondroitin sulfate, an intriguing polysaccharide from sea cucumber: past, present, and future.

Fucosylated chondroitin sulfate (FCS) is a unique polysaccharide, first described nearly four decades ago, and found exclusively in sea cucumbers. It is a component of the extracellular matrix, possibly associated with peculiar properties of the invertebrate tissue. The carbohydrate features a chondroitin sulfate core with branches of sulfated α-Fuc linked to position 3 of the β-GlcA.

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions.

Aggregation-primed molten globule conformers of the p53 core domain provide potential tools for studying p53C aggregation in cancer.

The functionality of the tumor suppressor p53 is altered in more than 50% of human cancers, and many individuals with cancer exhibit amyloid-like buildups of aggregated p53. An understanding of what triggers the pathogenic amyloid conversion of p53 is required for the further development of cancer therapies. Here, perturbation of the p53 core domain (p53C) with subdenaturing concentrations of guanidine hydrochloride and high hydrostatic pressure revealed native-like molten globule (MG) states, a subset of which were highly prone to amyloidogenic aggregation.