New publication from Dr. Linda Penn

Nov 5, 2019

Dr. Linda Penn

MBP researcher Dr. Linda Penn, has released a new article titled 'Multiple direct interactions of TBP with the MYC oncoprotein'. The study, published in Nature Structural and Molecular Biology, is a collaboration between scientists at Princess Margaret Cancer Center, including MBP researcher Dr. Brian Raught, and scientists at Linköping University, Sweden.


Figure from Linda Penn paper

"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 (TAF1TAND1). Using biochemical approaches, we have shown that MYC amino acids 115–124 also interact with TBP independently of TAF1TAND1. 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'.

This discovery may lead to the development of new cancer drugs that disrupt the function of MYC in tumor cells.

Read the full article here.