| Autor: |
Lau J; Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Centros, Singapore., Lew QJ, Diribarne G, Michels AA, Dey A, Bensaude O, Lane DP, Chao SH |
| Jazyk: |
angličtina |
| Zdroj: |
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2009 Jul 15; Vol. 8 (14), pp. 2247-54. |
| DOI: |
10.4161/cc.8.14.9015 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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