The A20-binding protein ABIN-2 exerts unexpected function in mediating transcriptional coactivation.
The human ABIN-2 was originally identified as an A20-associating cytosolic protein to block NF-kappaB activation induced by various stimuli. Here we report that ABIN-2 has the potential to enter the nucleus and plays a role in mediating transcriptional activation in both yeast and mammalian cells. The Gal4BD-ABIN-2 fusion protein is able to drive the expression of the GAL4-responsive reporter gene in yeast efficiently without the need of the Gal4p activation domain, suggesting that ABIN-2 functions as a transcriptional coactivator and facilitates transcription in yeast. In contrast to the activity in yeast, however, only the C-terminal fragment of ABIN-2 exerts the transactivating activity in mammalian cells but not the full-length ABIN-2 protein. This observation has led to the identification of the N-terminal 195 amino acids of ABIN-2 as a regulatory domain, which retains the full-length ABIN-2 in the cytoplasm of mammalian cells and thus cannot transactivate. We have also found that BAF60a, a component of chromatin-remodeling complex, interacts with ABIN-2 by the yeast two-hybrid analysis. Together, our results suggest that the nuclear ABIN-2 defines a novel transcriptional coactivator and acts presumably by recruiting a chromatin-remodeling complex to the site of the target gene.
Chien
Chia-Yi
CY
Department of Life Science, National Yang-Ming University, 112, ROC, Taipei, Taiwan.
Liu
Wei-Kuang
WK
Chou
Chen-Kung
CK
Su
Jin-Yuan
JY
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D006801:Humans; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C109786:SMARCD1 protein, human; C434062:TNIP2 protein, human; D014157:Transcription Factors