The BCA2 protein contains a RING H2 finger and a Zn finger near the N-terminus and has E3 ligase activity.
RING finger proteins play critical roles in mediating the transfer of ubiquitin and ubiquitin like modifiers to heterologous
substrates as well as to the RING finger proteins themselves. Protein modification by ubiquitin and small ubiquitin-related
modifier (SUMO) plays a pivotal role in protein homeostasis and is critical to regulating basic cellular processes such as
proliferation, differentiation, apoptosis, intracellular signaling, and gene-transcriptional regulation. The addition of
ubiquitin or SUMO can modulate the ability of proteins to interact with their partners, alter their patterns of sub-cellular
localization and control their stability. It is clear that SUMO influences many different biological processes however
recent data suggest that it is specifically important in the regulation of transcription. BCA2 is an E3 ligase that interacts
with the SUMO conjugating enzyme Ubc9. It could therefore function as an E3 in the sumoylation of various transcription
factors. We have found that the BCA2 is co-expressed with the estrogen receptor in 74% of ER-positive invasive ductal
carcinomas from a 635 member breast cancer cohort (p = 0.004). At the cellular level, BCA2 co-localizes with ER and it
appears that at the transcriptional level BCA2 mRNA expression is regulated by estrogen. Bioinformatic analysis of the
BCA2 promoter region revealed ER and PR binding sites as well as that of other more general transcription factors. The
data presented here provides an overview of the potential involvement of the BCA2 in hormone responsive breast cancer
and opens up avenues that should be exploited to better understand the regulation of ER expression, growth of breast
cancer cells, and the importance of BCA2.