Cdk9 phosphorylates Pirh2 protein and prevents degradation of p53 protein
| Autor: | Tinatin Chabrashvili, Asen Bagashev, Samuel Benchimol, Shongshan Fan, Bassel E. Sawaya, Pier Paolo Claudio, Ruma Mukerjee, Roger P Leng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Ubiquitin-Protein Ligases
Molecular Sequence Data Transfection Cell Line Ubiquitin Western blot RNA interference Report Protein Interaction Mapping Gene expression Transcriptional regulation medicine Humans Amino Acid Sequence Phosphorylation RNA Small Interfering Molecular Biology HIV Long Terminal Repeat biology medicine.diagnostic_test Ubiquitination Proto-Oncogene Proteins c-mdm2 Cell Biology Cyclin-Dependent Kinase 9 Molecular biology HIV-1 biology.protein Mdm2 RNA Interference Tumor Suppressor Protein p53 Developmental Biology |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.24733 |
| Popis: | Several reports have pointed to the negative involvement of p53 in transcriptional regulation of the human immunodeficiency virus type 1 long-terminal repeat (HIV-1 LTR). We recently demonstrated that through their physical interaction, cdk9 phosphorylates p53 on Ser-392, leading to p53 stability and accumulation. As a result, p53 stalled transcriptional elongation of the HIV-1 LTR and significantly reduced HIV-1 replication in primary microglia and astrocytes. Therefore, we sought to identify the mechanisms used by cdk9 to allow this p53 function. Using western blot analysis, we found that cdk9 promotes inhibition and phosphorylation of Mdm2 on Ser-395, thus preventing degradation of p53, a protein that is directly involved in promoting p53 ubiquitination. On the other hand, we showed that cdk9 phosphorylates Pirh2 on Ser-211 and Thr-217 residues through their physical interaction. Phosphorylation of Pirh2 renders it inactive and may contribute to p53-inhibition of transcriptional elongation of the HIV-1 LTR. Hence, we suggest that phosphorylation of Pirh2 may be a novel target for the inhibition of HIV-1 gene expression. |
| Databáze: | OpenAIRE |
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