SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation.
The Ski-interacting protein SKIP/SNW1 associates with the P-TEFb/CDK9 elongation factor and coactivates inducible genes, including HIV-1. We show here that SKIP also associates with c-Myc and Menin, a subunit of the MLL1 histone methyltransferase (H3K4me3) complex and that HIV-1 Tat transactivation requires c-Myc and Menin, but not MLL1 or H3K4me3. ... RNAi-ChIP experiments reveal that SKIP acts downstream of Tat:P-TEFb to recruit c-Myc and its partner TRRAP, a scaffold for histone acetyltransferases, to the HIV-1 promoter. By contrast, SKIP is recruited by the RNF20 H2B ubiquitin ligase to the basal HIV-1 promoter in a step that is bypassed by Tat and downregulated by c-Myc. Of interest, we find that SKIP and P-TEFb are dispensable for UV stress-induced HIV-1 transcription, which is strongly upregulated by treating cells with the CDK9 inhibitor flavopiridol. Thus, SKIP acts with c-Myc and Menin to promote HIV-1 Tat:P-TEFb transcription at an elongation step that is bypassed under stress.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cyclin T, Cyclin-Dependent Kinase 9, DNA Damage, DNA-Binding Proteins, Flavonoids, Gene Expression Regulation, Viral, HIV Long Terminal Repeat, Hela Cells, Histones, Humans, Methylation, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, Nuclear Receptor Coactivators, Piperidines, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, Protein Binding, Protein Interaction Domains and Motifs, Protein Kinase Inhibitors, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Transcription Factors, Transcriptional Activation, Ubiquitin-Protein Ligases, Ultraviolet Rays, tat Gene Products, Human Immunodeficiency Virus
Adaptor Proteins, Signal Transducing, Cyclin T, Cyclin-Dependent Kinase 9, DNA Damage, DNA-Binding Proteins, Flavonoids, Gene Expression Regulation, Viral, HIV Long Terminal Repeat, Hela Cells, Histones, Humans, Methylation, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, Nuclear Receptor Coactivators, Piperidines, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, Protein Binding, Protein Interaction Domains and Motifs, Protein Kinase Inhibitors, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Transcription Factors, Transcriptional Activation, Ubiquitin-Protein Ligases, Ultraviolet Rays, tat Gene Products, Human Immunodeficiency Virus
Mol. Cell
Date: Oct. 09, 2009
PubMed ID: 19818711
View in: Pubmed Google Scholar
Download Curated Data For This Publication
104746
Switch View:
- Interactions 16