Understanding the relationship between NUT and BET proteins in NMC

NUT has been found to fuse with bromodomain-containing proteins 3 and 4 (BRD3 and BRD4) in NUT midline carcinoma (NMC), a very rare, extremely aggressive, and genetically defined human cancer. NMC has recently been designated as a sub classification of poorly differentiated squamous cell carcinoma. In the majority of NMCs (~75%), most of the coding sequence is fused to form chimeric genes that encode BRD-NUT fusion proteins.

NUT - A Protein Coding Gene

The NUT gene is found on chromosome 15q14 and encodes for the NUT protein which is a key component of the RNA polymerase II Mediator complex. This multi-subunit assembly is required for all RNA pol II-dependent transcriptional activation, coordinating both nuclear and mitochondrial gene transcription. The complex also includes pol II, and transcription factors TFIIA-F. It serves as a central scaffold within the pre-initiation complex (PIC) responsible for converting biological stimuli (in the form of transcription factors) into gene expression responses.