The acidic C-terminal domain and A-box of HMGB-1 regulates p53-mediated transcription
Open Access
- 15 June 2003
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 31 (12), 3236-3247
- https://doi.org/10.1093/nar/gkg412
Abstract
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.Keywords
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