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[A. Biochemistry/Molecular Biology] A-19

The deubiquitinating enzyme BAP1 regulates BIRC5 in gastric

tumorigenesis

Jin Kim¹, Peter Chang-Whan Lee¹*

¹Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 05505, Korea

BAP1(BRCA1-associated protein1) which belongs to the family of ubiquitin carboxy-terminal hydrolases is related to
26S proteasome to removal of ubiquitin chain from target substrates. BIRC5 (also names Survivin) was previously

reported to be a member of the inhibitor of apoptosis (IAP) gene family, is known to play a pivotal role in
development of various types of malignant tumors.Here, we found that BAP1 and BIRC5 are frequently

overexpressed in gastric cancer (GC) patients. BAP1 interacts with BIRC5 and trims its ubiquitin chain, stabilizing
BIRC5 expression in a dose dependent manner in GC cells while knockdown of BAP1 accelerates BIRC5 protein

degradation. The loss of BIRC5 in gastric cancer cells significantly suppressed cell migration, and invasion by
interfering apoptosis signaling pathway-related genes. Our finding suggests that BAP1 and BIRC5 might be a

biomarker candidate and therapeutic targets gastric cancer.