Abstract
Nuclear factor (NF)-kappaB transcription factors are involved in the control of a large number of normal cellular and organismal processes, such as immune and inflammatory responses, developmental processes, cellular growth, and apoptosis. Transcription of the human immunodeficiency virus type 1 (HIV-1) genome depends on the intracellular environment where the integrate viral DNA is regulated by a complex interplay among viral regulatory proteins, such as Tat, and host cellular transcription factors, such as NF-kappaB, interacting with the viral long terminal repeat region. CBP (CREB-binding protein) and p300, containing an intrinsic histone acetyltransferase (HAT) activity, have emerged as coactivators for various DNA-binding transcription factors. Here, we show that the p50 subunit as well as the p50/p65 of NF-kappaB, and not other factors such as SP1, TFIIB, polymerase II, TFIIA, or p65, can be acetylated by CBP/p300 HAT domain. Acetylation of p50 was completely dependent on the presence of both HAT domain and Tat proteins, implying that Tat influences the transcription machinery by aiding CBP/p300 to acquire new partners and increase its functional repertoire. Three lysines, Lys-431, Lys-440, and Lys-441 in p50 were all acetylated in vitro, and a sequence similarity among p50, p53, Tat, and activin receptor type I on these particular lysines was observed. All proteins have been shown to be acetylated by the CBP/p300 HAT domain. Acetylated p50 increases its DNA binding properties, as evident by streptavidin/biotin pull-down assays when using labeled NF-kappaB oligonucleotides. Increased DNA binding on HIV-1 long terminal repeat coincided with increases in the rate of transcription. Therefore, we propose that acetylation of the DNA binding domain of NF-kappaB aids in nuclear translocation and enhanced transcription and also suggest that the substrate specificity of CBP/p300 can be altered by small peptide molecules, such as HIV-encoded Tat.
Highlights
The prototype Nuclear factor (NF)-B transcription factor consists of two subunits, NF-B1 (p50), the DNA-binding subunit, and RelA (p65), the transactivating subunit
The best studied Rel-IB interaction is that of IB ␣ with the Nuclear factor B (NF-B) p50-RelA dimer, and this interaction blocks the ability of NF-B to enter the nucleus and bind to DNA [4]
The p50 Subunit of NF-B Is Acetylated by the histone acetyltransferase (HAT) Domain of CBP/p300 —The human immunodeficiency virus type 1 (HIV-1) promoter has two NF-B binding sites in its enhancer region [19]
Summary
The prototype NF-B transcription factor consists of two subunits, NF-B1 (p50), the DNA-binding subunit, and RelA (p65), the transactivating subunit. We find that the p50 subunit of transcription factor NF-B is acetylated by CBP/p300 in presence of HIV-1 viral protein Tat. Interestingly, acetylated p50 or p50/p65 binds with higher affinity to DNA containing NF-B binding sites.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
