| http://purl.uniprot.org/citations/28842558 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28842558 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28842558 | http://www.w3.org/2000/01/rdf-schema#comment | "B lymphocyte-induced maturation protein-1 (Blimp-1) ensures B-cell differentiation into the plasma cell stage, and its instability constitutes a crucial oncogenic element in certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). However, the underlying degradation mechanisms and their possible therapeutic relevance remain unexplored. Here, we show that N-terminal misfolding mutations in ABC-DLBCL render Blimp-1 protein susceptible to proteasome-mediated degradation but spare its transcription-regulating activity. Mechanistically, whereas wild-type Blimp-1 metabolism is triggered in the nucleus through PML-mediated sumoylation, the degradation of lymphoma-associated mutants is accelerated by subversion of this pathway to Hrd1-mediated cytoplasmic sequestration and ubiquitination. Screening experiments identifies the heat shock protein 70 (HSP70) that selects Blimp-1 mutants for Hrd1 association, and HSP70 inhibition restores their nuclear accumulation and oncorepressor activities without disrupting normal B-cell maturation. Therefore, HSP70-Hrd1 axis represents a potential therapeutic target for restoring the oncorepressor activity of unstable lymphoma-associated Blimp-1 mutants.The transcriptional repressor Blimp-1 has an important role in B-cell differentiation. Here the authors show that lymphoma-associated Blimp-1 mutants are selectively recognized by HSP70-Hrd1, which leads to their accelerated degradation and propose HSP70 inhibition as a therapeutic approach for certain lymphomas."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-017-00476-w"xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-017-00476-w"xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Lin J."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Lin J."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Meng G."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Meng G."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhang W."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhang W."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Xia Y."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Xia Y."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Yan L."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Yan L."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhu J."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhu J."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhao Y.L."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Zhao Y.L."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Li J.Y."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Li J.Y."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Liu L.X."xsd:string |
| http://purl.uniprot.org/citations/28842558 | http://purl.uniprot.org/core/author | "Liu L.X."xsd:string |