| http://purl.uniprot.org/citations/25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25535389 | http://www.w3.org/2000/01/rdf-schema#comment | "The MAP kinase TGFβ-activated kinase (TAK1) plays a crucial role in physiologic and pathologic cellular functions including cell survival, differentiation, apoptosis, inflammation, and oncogenesis. However, the entire repertoire of its mechanism of action has not been elucidated. Here, we found that ablation of Tak1 in myeloid cells causes osteopetrosis in mice as a result of defective osteoclastogenesis. Mechanistically, Tak1 deficiency correlated with increased NUMB-like (NUMBL) levels. Accordingly, forced expression of Numbl abrogated osteoclastogenesis whereas its deletion partially restored osteoclastogenesis and reversed the phenotype of Tak1 deficiency. Tak1 deletion also down-regulated Notch intracellular domain (NICD), but increased the levels of the transcription factor recombinant recognition sequence binding protein at Jκ site (RBPJ), consistent with NUMBL regulating notch signaling through degradation of NICD, a modulator of RBPJ. Accordingly, deletion of Rbpj partially corrected osteopetrosis in Tak1-deficient mice. Furthermore, expression of active IKK2 in RBPJ/TAK1-deficient cells significantly restored osteoclastogenesis, indicating that activation of NF-κB is essential for complete rescue of the pathway. Thus, we propose that TAK1 regulates osteoclastogenesis by integrating activation of NF-κB and derepression of NOTCH/RBPJ in myeloid cells through inhibition of NUMBL."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1415213112"xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/author | "Abu-Amer Y."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/author | "Chen T.H."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/author | "Mbalaviele G."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/author | "Swarnkar G."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/author | "Karuppaiah K."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/pages | "154-159"xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/title | "Osteopetrosis in TAK1-deficient mice owing to defective NF-kappaB and NOTCH signaling."xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://purl.uniprot.org/core/volume | "112"xsd:string |
| http://purl.uniprot.org/citations/25535389 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25535389 |
| http://purl.uniprot.org/citations/25535389 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25535389 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGK6-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_D3Z7I6-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_D3Z7J1-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YTV5-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A0A077S2U6-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_D3Z1E8-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YVE0-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A0A1Y7VJJ7-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A2AP92-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |
| http://purl.uniprot.org/uniprot/#_A2AP93-mappedCitation-25535389 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25535389 |