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-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.
Mesh Terms:
Binding Sites, Casein Kinase II, Cell Line, Tumor, Cell Transformation, Neoplastic, Chemokine CXCL10, Co-Repressor Proteins, Esophageal Neoplasms, Gene Expression Regulation, Neoplastic, Histone Deacetylases, Humans, JNK Mitogen-Activated Protein Kinases, Neoplasm Invasiveness, Nuclear Receptor Co-Repressor 1, Promoter Regions, Genetic, Protein Binding, Proteolysis, Signal Transduction, Transcription, Genetic
Mol. Biol. Cell
Date: Aug. 01, 2012
Download Curated Data For This Publication
154737
Switch View:
  • Interactions 3
  • PTM Genes 1