Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The three FET (FUS, EWSR1, and TAF15) family RNA binding proteins are expressed in all tissues and almost all cell types. The disordered N-terminal parts are always present in FET fusion oncoproteins of sarcomas and leukemia. Mutations in FUS and TAF15 cause aggregation of FET proteins in neurological disorders. Here we used recombinant proteins in pulldown experiments and mass spectrometry to identify major interaction partners of the FET N-terminal parts. We report that FUS, EWSR1, and TAF15 form homo- and heterocomplexes as major binding partners and identify an evolutionarily conserved N-terminal motif (FETBM1) that is required for this interaction. The binding is RNA and DNA independent and robust up to 1 M of NaCl. The localization of FETBM1 and its target sequences supports a simple model for FET protein aggregation as reported in neurological disorders such as amyotrophic lateral sclerosis, frontotemporal dementia, and essential tremor. The FETBM1 localization also explains the binding of normal full-length FET proteins to their oncogenic fusion proteins.
 ...
PMID:A conserved N-terminal motif is required for complex formation between FUS, EWSR1, TAF15 and their oncogenic fusion proteins. 2397 37

Neurodegenerative disorders such as Alzheimer disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Parkinson disease (PD), Huntington's disease (HD), and multiple sclerosis (MS) affect different neuronal cells, and have a variable age of onset, clinical symptoms, and pathological features. Despite the great progress in understanding the etiology of these disorders, the underlying mechanisms remain largely unclear. Among the processes affected in neurodegenerative diseases, alteration in RNA metabolism is emerging as a crucial player. RNA-binding proteins (RBPs) are involved at all stages of RNA metabolism and display a broad range of functions, including modulation of mRNA transcription, splicing, editing, export, stability, translation and localization and miRNA biogenesis, thus enormously impacting regulation of gene expression. On the other hand, aberrant regulation of RBP expression or activity can contribute to disease onset and progression. Recent reports identified mutations causative of neurological disorders in the genes encoding a family of RBPs named FET (FUS/TLS, EWS and TAF15). This review summarizes recent works documenting the involvement of FET proteins in the pathology of ALS, FTLD, essential tremor (ET) and other neurodegenerative diseases. Moreover, clinical implications of recent advances in FET research are critically discussed.
 ...
PMID:Role of FET proteins in neurodegenerative disorders. 2741 68