학술논문
Multiple direct interactions of TBP with the MYC oncoprotein
TATA-binding protein
TATA-binding protein
Document Type
Report
Author
Source
Nature Structural and Molecular Biology. November 2019, Vol. 26 Issue 11, p1035, 9 p.
Subject
Language
English
ISSN
1545-9993
Abstract
Author(s): Yong Wei [sup.1] [sup.2] [sup.3] , Diana Resetca [sup.2] [sup.4] , Zhe Li [sup.5] , Isak Johansson-Åkhe [sup.1] , Alexandra Ahlner [sup.1] , Sara Helander [sup.1] , Amelie Wallenhammar [...]
Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -Å resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1.sup.TAND1). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1.sup.TAND1. Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly. Structural, biophysical and modeling approaches, combined with cell-based assays, reveal how the oncogenic transcription factor MYC interacts with subunits of the general transcription factor TFIID to modulate gene expression.
Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -Å resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1.sup.TAND1). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1.sup.TAND1. Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly. Structural, biophysical and modeling approaches, combined with cell-based assays, reveal how the oncogenic transcription factor MYC interacts with subunits of the general transcription factor TFIID to modulate gene expression.