分子醫學研究所HUANG, JING-YIJING-YIHUANGSHEN, BIN-JONBIN-JONSHENTSAI, WEN-HAIWEN-HAITSAILEE, SHENG-CHUNGSHENG-CHUNGLEE2008-12-292018-07-092008-12-292018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/95089Hepatitis B virus X-associated protein (HBXAP) is a plant homeodomain ( PHD) finger-containing protein implicated in transcription regulation. However, the underlying molecular mechanism remains to be defined. Here, we show that HBXAP represses NF-kappaB-mediated gene activation in a dose- dependent manner. Our results showed that HBXAP and NF- kappaB colocalize to the nuclear matrix with specific physical interaction between them. HBXAP may depend on its nuclear matrix localization for its repression of NF-kappaB- mediated gene repression. A specific nuclear matrix targeting sequence of HBXAP was identified. The sequence is included in a region encompassing amino acids 688-722 that could form a coiled-coil structure. The 18-amino acid stretch lies at the core of that structure. The present results showed that either the coiled-coil conformation or the PHD finger domain is crucial for the transcription repression activity of HBXAP on NF -kappaB-mediated gene activation. Taken together, our results suggest that HBXAP may function as a negative regulator for TNF-alpha-induced, NF- kappaB-mediated gene activation. (C) 2004 Elsevier Inc. All rights reserved.en-USHBXAPNF-kappa Bnuclear matrixp50p65PHD[SDGs]SDG3