Section 55
Chapter 54,682

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

Yoo, J.-Y.; Choi, H.-K.; Choi, K.-C.; Park, S.-Y.; Ota, I.; Yook, J.I.; Lee, Y.-H.; Kim, K.; Yoon, H.-G.

Molecular Biology of the Cell 23(15): 2943-2954


ISSN/ISBN: 1939-4586
PMID: 22675025
DOI: 10.1091/mbc.e11-11-0947
Accession: 054681258

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.

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