| http://purl.uniprot.org/citations/25410660 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25410660 | http://www.w3.org/2000/01/rdf-schema#comment | "Cytosolic accumulation of TAR DNA binding protein 43 (TDP-43) is a major neuropathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms involved in TDP-43 accumulation remain largely unknown. Previously, we reported that inhibitors of cyclin-dependent kinases (CDKs) prevented cytosolic stress granule accumulation of TDP-43, correlating with depletion of heterogeneous ribonucleoprotein (hnRNP) K from stress granules. In the present study, we further investigated the relationship between TDP-43 and hnRNP K and their control by CDKs. Inhibition of CDK2 abrogated the accumulation of TDP-43 into stress granules. Phosphorylated CDK2 co-localized with accumulated TDP-43 and phosphorylated hnRNP K in stress granules. Inhibition of CDK2 phosphorylation blocked phosphorylation of hnRNP K, preventing its incorporation into stress granules. Due to interaction between hnRNP K with TDP-43, the loss of hnRNP K from stress granules prevented accumulation of TDP-43. Mutation of Ser216 and Ser284 phosphorylation sites on hnRNP K inhibited hnRNP K- and TDP-43-positive stress granule formation in transfected cells. The interaction between hnRNP K and TDP-43 was further confirmed by the loss of TDP-43 accumulation following siRNA-mediated inhibition of hnRNP K expression. A substantial decrease of CDK2 and hnRNP K expression in spinal cord motor neurons in ALS patients demonstrates a potential key role for these proteins in ALS and TDP-43 accumulation, indicating that further investigation of the association between hnRNP K and TDP-43 is warranted. Understanding how kinase activity modulates TDP-43 accumulation may provide new pharmacological targets for disease intervention."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddu578"xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Yang S."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Zhang K."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "White A.R."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Boeckers T.M."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Proepper C."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Atkin J.D."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Crouch P.J."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Turner B.J."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Duncan C."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Blair I."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "James J.L."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Caragounis A."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Liddell J.R."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Grubman A."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Moujalled D."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Moujalled D.M."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Kanninen K.M."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Parker S.J."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/author | "Lidgerwood G."xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/25410660 | http://purl.uniprot.org/core/pages | "1655-1669"xsd:string |