Functional interaction between nuclear matrix-associated HBXAP and NF-kappaB.
Hepatitis 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.
Huang
Jing-Yi
JY
Institute of Molecular Medicine, National Taiwan University, Taipei.
Shen
Bin-Jon
BJ
Tsai
Wen-Hai
WH
Lee
Sheng-Chung
SC
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D015530:Nuclear Matrix / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D009687:Nuclear Proteins; C452851:RSF1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha