| http://purl.uniprot.org/citations/28674184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28674184 | http://www.w3.org/2000/01/rdf-schema#comment | "Although deregulation of MEK/extracellular signal-regulated kinase (ERK) activity is a key feature in cancer, high-magnitude MEK/ERK activity can paradoxically induce growth inhibition. Therefore, additional mechanisms may exist to modulate MEK/ERK activity in favor of tumor cell proliferation. We previously reported that mortalin/HSPA9 can facilitate proliferation of certain KRAS and BRAF tumor cells by modulating MEK/ERK activity. In this study, we demonstrated that mortalin can regulate MEK/ERK activity via protein phosphatase 1α (PP1α). We found that PP1α inhibition increases steady-state levels of phosphorylated MEK1/2 in various tumor cells expressing B-RafV600E or K-RasG12C/D Intriguingly, coimmunoprecipitation and in vitro binding assays revealed that mortalin facilitates PP1α-mediated MEK1/2 dephosphorylation by promoting PP1α-MEK1/2 interaction in an ATP-sensitive manner. The region spanning Val482 to Glu491 in the substrate-binding cavity and the substrate lid of mortalin were necessary for these physical interactions, which is consistent with conventional heat shock protein 70 (HSP70)-client interaction mechanisms. Nevertheless, mortalin depletion did not affect cellular PP1α levels or its regulatory phosphorylation, suggesting a nonconventional role for mortalin in promoting PP1α-MEK1/2 interaction. Of note, PP1α was upregulated in human melanoma and pancreatic cancer biopsy specimens in correlation with mortalin upregulation. PP1α may therefore have a role in tumorigenesis in concert with mortalin, which affects MEK/ERK activity in tumor cells."xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00061-17"xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/author | "Hong S.K."xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/author | "Park J.I."xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/author | "Wu P.K."xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/pages | "e00061-17"xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/title | "Steady-State Levels of Phosphorylated Mitogen-Activated Protein Kinase Kinase 1/2 Determined by Mortalin/HSPA9 and Protein Phosphatase 1 Alpha in KRAS and BRAF Tumor Cells."xsd:string |
| http://purl.uniprot.org/citations/28674184 | http://purl.uniprot.org/core/volume | "37"xsd:string |
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