Bromodomain-containing protein 3

Bromodomain-containing protein 3 (BRD3) also known as RING3-like protein (RING3L) is a is_associated_with::protein that in humans is encoded by the BRD3 is_associated_with::gene. This gene was identified based on its homology to the gene encoding the RING3 (is_associated_with::BRD2) is_associated_with::protein, a is_associated_with::serine/threonine kinase. The gene localizes to 9q34, a region which contains several is_associated_with::major histocompatibility complex (MHC) genes.

Structure
BRD3 is a member of the Bromodmain and Extra-Terminal motif (BET) protein family. Like other BET family members it contains two tandem homologous is_associated_with::bromodomains and an "Extra-Terminal" motif.

BRD3, similar to BRD2, does not have a long C-terminal domain as BET family proteins is_associated_with::BRD4 and is_associated_with::BRDT do.

Function
BRD3 is a member of the BET (is_associated_with::Bromodomain and Extra-Terminal motif) protein family. Like other BET protein family members, BRD3 associates with is_associated_with::acetylated is_associated_with::lysine residues on is_associated_with::histones and is_associated_with::transcription factors.

BRD3 has been implicated in nucleosome remodeling in the context of transcription.

BRD2 and BRD3 perform overlapping cellular functions.

Clinical significance
Chromosomal translocation of BRD3 with the NUT gene has been implicated in is_associated_with::NUT midline carcinoma. BRD3-NUT driven cancers are histopathologically indistiguishable from BRD4-NUT driven cancers, likely because these translocations involve the N-terminal portion is_associated_with::bromodomain-containing portion of these proteins which are highly conserved.

Depletion of BRD3 slows growth in cancer models including is_associated_with::prostate cancer and is_associated_with::medulloblastoma. The effect of BRD3 depletion is milder than that of other BET proteins is_associated_with::BRD2 and is_associated_with::BRD4 when each is tested in isolation. is_associated_with::BET inhibitors target highly conserved BET bromodomains and displace BRD2, BRD3, and BRD4 from chromatin simultaneously. Functional redundancy between BRD2 and BRD3 suggests that their simultaneous disruption of these proteins may be more important than is appreciated by depletion of these proteins individually.