XXXX -responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis.

@entity745 @entity2000 @entity2655 @entity72156 @entity460 @entity238
BACKGROUND: Mutations in @entity460 -responsive transactivator (CREST) encoding gene have been recently linked to @entity2655 . Similar to several proteins implicated in @entity2655 , CREST contains a prion-like domain and was reported to be a component of paraspeckles. RESULTS: We demonstrate that CREST is prone to aggregation and co-aggregates with FUS but not with other two @entity2655 , @entity745 and TAF15, in cultured cells. Aggregation of CREST affects paraspeckle integrity, probably by trapping other paraspeckle proteins within aggregates. Like several other @entity2655 -associated proteins, CREST is recruited to induced stress granules. Neither of the CREST mutations described in @entity2655 alters its subcellular localization, stress granule recruitment or detergent solubility; however @entity72156 mutation results in elevated steady-state levels and more frequent nuclear aggregation of the protein. Both wild-type protein and its mutants negatively affect neurite network complexity of unstimulated cultured neurons when overexpressed, with @entity72156 mutation being the most deleterious. When overexpressed in the @entity238 eye, wild-type CREST or its mutants lead to severe @entity2000 without obvious differences between the variants. CONCLUSIONS: Our data indicate that CREST and certain other @entity2655 share several features implicated in @entity2655 pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis.
