http://purl.uniprot.org/citations/28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/28739871 | http://www.w3.org/2000/01/rdf-schema#comment | "The Hippo pathway is an evolutionarily conserved signaling pathway that plays important roles in stem cell biology, tissue homeostasis, and cancer development. Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo-Yes-associated protein (YAP) pathway. Vgll4 inhibits cell proliferation and tumor growth by competing with YAP for binding to TEA-domain proteins (TEADs). However, the mechanisms by which Vgll4 itself is regulated are unclear. Here we identified a mechanism that regulates Vgll4's tumor-suppressing function. We found that Vgll4 is phosphorylated in vitro and in vivo by cyclin-dependent kinase 1 (CDK1) during antimitotic drug-induced mitotic arrest and also in normal mitosis. We further identified Ser-58, Ser-155, Thr-159, and Ser-280 as the main mitotic phosphorylation sites in Vgll4. We also noted that the nonphosphorylatable mutant Vgll4-4A (S58A/S155A/T159A/S280A) suppressed tumorigenesis in pancreatic cancer cells in vitro and in vivo to a greater extent than did wild-type Vgll4, suggesting that mitotic phosphorylation inhibits Vgll4's tumor-suppressive activity. Consistent with these observations, the Vgll4-4A mutant possessed higher-binding affinity to TEAD1 than wild-type Vgll4. Interestingly, Vgll4 and Vgll4-4A markedly suppressed YAP and β-catenin signaling activity. Together, these findings reveal a previously unrecognized mechanism for Vgll4 regulation in mitosis and its role in tumorigenesis."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m117.796284"xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Dong J."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Zhou J."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Zeng Y."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/author | "Stauffer S."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/pages | "15028-15038"xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/title | "Cyclin-dependent kinase 1 (CDK1)-mediated mitotic phosphorylation of the transcriptional co-repressor Vgll4 inhibits its tumor-suppressing activity."xsd:string |
http://purl.uniprot.org/citations/28739871 | http://purl.uniprot.org/core/volume | "292"xsd:string |
http://purl.uniprot.org/citations/28739871 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28739871 |
http://purl.uniprot.org/citations/28739871 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28739871 |
http://purl.uniprot.org/uniprot/#_A0A0A6YYI5-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_A0A075B6E4-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_Q14135-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_G5E9M7-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_G5E9M9-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_Q0H0I4-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/#_Q0H0I7-mappedCitation-28739871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/Q0H0I7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28739871 |
http://purl.uniprot.org/uniprot/Q14135 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28739871 |