Functional interaction of the c-Myc transactivation domain with the TATA binding protein: evidence for an induced fit model of transactivation domain folding - PubMed (original) (raw)
. 1996 Jul 23;35(29):9584-93.
doi: 10.1021/bi960793v.
Affiliations
- PMID: 8755740
- DOI: 10.1021/bi960793v
Functional interaction of the c-Myc transactivation domain with the TATA binding protein: evidence for an induced fit model of transactivation domain folding
I J McEwan et al. Biochemistry. 1996.
Abstract
c-Myc is a member of a family of sequence specific-DNA binding proteins that are thought to regulate the transcription of genes involved in normal cell growth, differentiation, and apoptosis. In order to understand how human c-myc functions as a transcription factor, we have studied the mechanism of action and structure of the N-terminal transactivation domain, amino acids 1-143. In a protein interaction assay, c-myc1-143 bound selectively to two basal transcription factors, the TATA binding protein (TBP) and the RAP74 subunit of TFIIF. Furthermore, the isolated c-myc transactivation domain competed for limiting factors required for the assembly of a functional preinitiation complex. This squelching of basal transcription was reversed in a dose-dependent manner by recombinant TBP. Taken together, these results identify TBP as an important target for the c-myc transactivation domain, during transcriptional initiation. Similar to other transactivation domains, the c-myc1-143 polypeptide showed little or no evidence of secondary structure, when measured by circular dichroism spectroscopy (CD) in aqueous solution. However, significant alpha-helical conformation was observed in the presence of the hydrophobic solvent trifluoroethanol. Strikingly, addition of TBP caused changes in the CD spectra consistent with induction of protein conformation in c-myc1-143 during interaction with the target factor. This change was specific for TBP as a similar effect was not observed in the presence of TFIIB. These data support a model in which target factors induce or stabilize a structural conformation in activator proteins during transcriptional transactivation.
Similar articles
- N and C-terminal sub-regions in the c-Myc transactivation region and their joint role in creating versatility in folding and binding.
Fladvad M, Zhou K, Moshref A, Pursglove S, Säfsten P, Sunnerhagen M. Fladvad M, et al. J Mol Biol. 2005 Feb 11;346(1):175-89. doi: 10.1016/j.jmb.2004.11.029. Epub 2004 Dec 10. J Mol Biol. 2005. PMID: 15663936 - Exon 4-encoded acidic domain in the epithelium-restricted Ets factor, ESX, confers potent transactivating capacity and binds to TATA-binding protein (TBP).
Chang CH, Scott GK, Baldwin MA, Benz CC. Chang CH, et al. Oncogene. 1999 Jun 24;18(25):3682-95. doi: 10.1038/sj.onc.1202674. Oncogene. 1999. PMID: 10391676 - The basal transcription factors TBP and TFB from the mesophilic archaeon Methanosarcina mazeii: structure and conformational changes upon interaction with stress-gene promoters.
Thomsen J, De Biase A, Kaczanowski S, Macario AJ, Thomm M, Zielenkiewicz P, MacColl R, Conway de Macario E. Thomsen J, et al. J Mol Biol. 2001 Jun 8;309(3):589-603. doi: 10.1006/jmbi.2001.4705. J Mol Biol. 2001. PMID: 11397082 - Mechanisms of transcriptional activation and repression can both involve TFIID.
Manley JL, Um M, Li C, Ashali H. Manley JL, et al. Philos Trans R Soc Lond B Biol Sci. 1996 Apr 29;351(1339):517-26. doi: 10.1098/rstb.1996.0050. Philos Trans R Soc Lond B Biol Sci. 1996. PMID: 8735274 Review. - X-ray crystallographic studies of eukaryotic transcription initiation factors.
Burley SK. Burley SK. Philos Trans R Soc Lond B Biol Sci. 1996 Apr 29;351(1339):483-9. doi: 10.1098/rstb.1996.0046. Philos Trans R Soc Lond B Biol Sci. 1996. PMID: 8735270 Review.
Cited by
- MYC phase separation selectively modulates the transcriptome.
Yang J, Chung CI, Koach J, Liu H, Navalkar A, He H, Ma Z, Zhao Q, Yang X, He L, Mittag T, Shen Y, Weiss WA, Shu X. Yang J, et al. Nat Struct Mol Biol. 2024 Oct;31(10):1567-1579. doi: 10.1038/s41594-024-01322-6. Epub 2024 May 29. Nat Struct Mol Biol. 2024. PMID: 38811792 - Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells.
Moyers BA, Partridge EC, Mackiewicz M, Betti MJ, Darji R, Meadows SK, Newberry KM, Brandsmeier LA, Wold BJ, Mendenhall EM, Myers RM. Moyers BA, et al. Genome Res. 2023 Dec 1;33(11):1879-1892. doi: 10.1101/gr.278205.123. Genome Res. 2023. PMID: 37852782 Free PMC article. - MYC amplifies gene expression through global changes in transcription factor dynamics.
Patange S, Ball DA, Wan Y, Karpova TS, Girvan M, Levens D, Larson DR. Patange S, et al. Cell Rep. 2022 Jan 25;38(4):110292. doi: 10.1016/j.celrep.2021.110292. Cell Rep. 2022. PMID: 35081348 Free PMC article. - Differential Transcriptional Reprogramming by Wild Type and Lymphoma-Associated Mutant MYC Proteins as B-Cells Convert to a Lymphoma Phenotype.
Mahani A, Arvidsson G, Sadeghi L, Grandien A, Wright APH. Mahani A, et al. Cancers (Basel). 2021 Dec 3;13(23):6093. doi: 10.3390/cancers13236093. Cancers (Basel). 2021. PMID: 34885204 Free PMC article. - MYC protein interactors in gene transcription and cancer.
Lourenco C, Resetca D, Redel C, Lin P, MacDonald AS, Ciaccio R, Kenney TMG, Wei Y, Andrews DW, Sunnerhagen M, Arrowsmith CH, Raught B, Penn LZ. Lourenco C, et al. Nat Rev Cancer. 2021 Sep;21(9):579-591. doi: 10.1038/s41568-021-00367-9. Epub 2021 Jun 29. Nat Rev Cancer. 2021. PMID: 34188192 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases