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.
Brès
Vanessa
V
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037-1099, USA.
Yoshida
Tomonori
T
Pickle
Loni
L
Jones
Katherine A
KA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D056906:Cyclin T / Q000235:genetics / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016325:HIV Long Terminal Repeat / Q000502:physiology; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D042925:Positive Transcriptional Elongation Factor B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D014466:Ultraviolet Rays; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C485622:ASH2L protein, human; D048868:Adaptor Proteins, Signal Transducing; C503684:CCNT1 protein, human; D056906:Cyclin T; D004268:DNA-Binding Proteins; D005419:Flavonoids; D006657:Histones; C497422:KMT2A protein, human; C105373:MEN1 protein, human; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C111791:SNW1 protein, human; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C113829:transformation-transcription domain-associated protein; D051788:Myeloid-Lymphoid Leukemia Protein; C077990:alvocidib; D011495:Histone-Lysine N-Methyltransferase; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases; D042925:Positive Transcriptional Elongation Factor B; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9