KMID : 0624620100430120807
|
|
BMB Reports 2010 Volume.43 No. 12 p.807 ~ p.812
|
|
ZAS3 represses NF¥êB-dependent transcription by direct competition for DNA binding
|
|
Hong Joung-Woo
Wu Lai-Chu
|
|
Abstract
|
|
|
NF¥êB and ZAS3 are transcription factors that control important cellular processes including immunity, cell survival and apoptosis. Although both proteins bind the ¥êB-motif, they produce opposite physiological consequences; NF¥êB activates transcription, promotes cell growth and is often found to be constitutively expressed in cancer cells, while ZAS3 generally represses transcription, inhibits cell proliferation and is downregulated in some cancers. Here, we show that ZAS3 inhibits NF¥êB-dependent transcription by competing with NF¥êB for the ¥êB-motif. Transient transfection studies show that N-terminal 645 amino acids is sufficient to repress transcription activated by NF¥êB, and that the identical region also possesses intrinsic repression activity to inhibit basal transcription from a promoter. Finally, in vitro DNA-protein interaction analysis shows that ZAS3 is able to displace NF¥êB by competing with NF¥êB for the ¥êB-motif. It is conceivable that ZAS3 has therapeutic potential for controlling aberrant activation of NF¥êB in various diseases.
|
|
KEYWORD
|
|
DNA competition, ¥êB-motif-binding proteins, NF¥êB, Transcriptional repression, ZAS3
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|