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.
Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Jung-Yoon
JY
Yoo
Hyo-Kyoung
HK
Choi
Kyung-Chul
KC
Choi
Soo-Yeon
SY
Park
Ichiro
I
Ota
Jong In
JI
Yook
Yoo-Hyun
YH
Lee
Kunhong
K
Kim
Ho-Geun
HG
Yoon
D001665:Binding Sites; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D059748:Proteolysis; D015398:Signal Transduction; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
D047390:Casein Kinase II; D054357:Chemokine CXCL10; D056970:Co-Repressor Proteins; D006655:Histone Deacetylases; D048031:JNK Mitogen-Activated Protein Kinases; D056971:Nuclear Receptor Co-Repressor 1; D000099186:Histone Deacetylase 3; C114753:CXCL10 protein, human; C539127:NCOR1 protein, human