Ubiquitination of HEXIM1 by HDM2.
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is an inhibitor of the positive transcription elongation factor b (P-TEFb), which controls RNA polymerase II transcription and human immunodeficiency virus Tat transactivation. In cells, more than half of P-TEFb is associated with HEXIM1 resulting in the inactivation of P-TEFb. Recently, we found that ... nucleophosmin (NPM), a key factor involved in p53 signaling pathway, interacts with HEXIM1 and activates P-TEFb-dependent transcription. Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1. However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation. Fusion of ubiquitin to HEXIM1 demonstrates stronger inhibition on P-TEFb-dependent transcription. Our results demonstrate that HDM2 functions as a specific E3 ubiquitin ligase for HEXIM1, suggesting a possible role for HEXIM1 ubiquitination in the regulation of P-TEFb activity.
Mesh Terms:
Cell Line, Cysteine Proteinase Inhibitors, Humans, Leupeptins, Nuclear Proteins, Positive Transcriptional Elongation Factor B, Proto-Oncogene Proteins c-mdm2, RNA-Binding Proteins, Signal Transduction, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination
Cell Line, Cysteine Proteinase Inhibitors, Humans, Leupeptins, Nuclear Proteins, Positive Transcriptional Elongation Factor B, Proto-Oncogene Proteins c-mdm2, RNA-Binding Proteins, Signal Transduction, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, Ubiquitination
Cell Cycle
Date: Jul. 15, 2009
PubMed ID: 19617712
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- Interactions 2
- PTM Genes 1