Cargando…

Nuclear hormone receptor corepressor promotes esophageal cancer cell invasion by transcriptional repression of interferon-γ–inducible protein 10 in a casein kinase 2–dependent manner

Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2α phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser...

Descripción completa

Detalles Bibliográficos
Autores principales: Yoo, Jung-Yoon, Choi, Hyo-Kyoung, Choi, Kyung-Chul, Park, Soo-Yeon, Ota, Ichiro, Yook, Jong In, Lee, Yoo-Hyun, Kim, Kunhong, Yoon, Ho-Geun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408420/
https://www.ncbi.nlm.nih.gov/pubmed/22675025
http://dx.doi.org/10.1091/mbc.E11-11-0947
Descripción
Sumario:Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2α phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser-2436 to stabilize the NCoR against the ubiquitin-dependent proteasomal degradation pathway. Importantly, NCoR promoted the invasion of esophageal cancer cells in a CK2-dependent manner. By using cyclic DNA microarray analysis, we identified CXCL10/IP-10 as a novel CK2α-NCoR cascade–regulated gene. The depletion of both NCoR and HDAC3 commonly derepressed IP-10 transcription, demonstrating the functional engagement of the NCoR-HDAC3 axis in IP-10 transcriptional repression. Furthermore, chromatin immunoprecipitation assays showed that c-Jun recruits NCoR-HDAC3 corepressor complexes to the (AP1 site of IP-10, leading to histone hypoacetylation and IP-10 down-regulation. Collectively these data suggest that the CK2α-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells.