This entry represents the short highly conserved C-terminal domain of certain bromodomain proteins, notably Brd4. The Brd4 CTD interacts with the cyclin T1 and Cdk9 subunits of positive transcription elongation factor b (pTEFb) complex. Brd4 displaces negative regulators, the HEXIM1 and 7SKsnRNA complex, from pTEFb, thereby transforming it into an active form that can phosphorylate RNA pol II [, ].
The gene encoding Nuclear Testis (NUT) protein is found fused to BRD3 or BRD4 genes in some aggressive types of carcinoma due to chromosomal translocations [, ]. Proteins of the BRD family contain two bromodomains that bind transcriptionally active chromatin through associations with acetylated histones H3 and H4 [, ]. Such proteins are crucial for the regulation of cell cycle progression. On the other hand, little is known about NUT protein function. NUT has a Nuclear Export Sequence (NES) as well as a Nuclear Localization Signal (NLS), both located towards the C-terminal end of the protein [, ]. A fused NUT-GFP protein has shown either cytoplasmic or nuclear localisation, suggesting that it is subject to nuclear/cytoplasmic shuttling. Consistent with this possibility, treatment with leptomycin B, an inhibitor of CRM1-dependent nuclear export, has been shown to result in re-distribution of NUT-GFP to the nucleus [, ].
This domain is found in the N-terminal region of Nuclear Testis (NUT) proteins. The NUT gene is found fused to BRD3 or BRD4 genes in some aggressive types of carcinoma, due to chromosomal translocations [, ]. The BRD family proteins contain two bromodomains that bind transcriptionally active chromatin through associations with acetylated histones H3 and H4 [, ]. BRD proteins are crucial for the regulation of cell cycle progression. The function of NUT proteins is not clear. NUT proteins contain the Nuclear Export Sequence (NES) and the Nuclear Localisation Signal (NLS), both located towards the C-terminal end of the protein [, ]. NUT-GFP protein showed either cytoplasmic or nuclear localisation, suggesting that it is subject to nuclear/cytoplasmic shuttling. Consistent with this possibility, treatment with leptomycin B an inhibitor of CRM1-dependent nuclear export resulted in re-distribution of NUT-GFP to the nucleus [, ]. Inspection of NUT revealed a C-terminal sequence similar to known nuclear export NUT protein carries some natively unstructured sequence.
