The acidic C-terminal domain and A-box of HMGB-1 regulates p53-mediated transcription.
p53 function is modulated by several covalent and non-covalent modifiers. The architectural DNA- binding protein, High Mobility Group protein B-1 is a unique activator of p53. HMGB-1 protein is structured into two HMG-box domains, namely A-box and B-box, connected to a long highly acidic C-terminal domain. Here we report that both the C-terminal domain and A-box of HMGB-1 are critical for stimulation of p53-mediated DNA binding to its cognate site. Though deletion of these domains showed minimal effect in activation of p53-mediated transcription from the DNA template as compared to full-length HMGB-1, truncation of both the domains indeed showed significant reduction of transcriptional activation from the chromatin template as observed in DNA binding. Using transient transfection assays we showed that the C-terminal acidic domain and A-box of HMGB-1 are critical for the enhancement of the p53-mediated transactivation in vivo. Furthermore, the C-terminal domain and A-box deleted HMGB-1 could not activate p53-dependent apoptosis above the basal level. In conclusion, these results elucidate the role of acidic C-terminal domain and A-box of HMGB-1 in p53-mediated transcriptional activation and its further downstream effect.
Banerjee
Sourav
S
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Kundu
Tapas K
TK
D017209:Apoptosis; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D024243:HMGB1 Protein / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D024243:HMGB1 Protein; D016159:Tumor Suppressor Protein p53; D004247:DNA