Wu W, Song W, Li S, Ouyang S, Fok KL, Diao R, Miao S, Chan HC, Wang L

YWK-II protein/APLP2 is a member of an evolutionarily conserved protein family that includes amyloid precursor protein (APP) and amyloid precursor like protein-1 (APLP1). We have previously demonstrated that YWK-II/APLP2 functions as a novel G(0)-protein-coupled receptor for Muellerian inhibiting substance (MIS) in cell survival. However, factors regulating the stability and turnover ...

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of YWK-II/APLP2 have not been identified. Here we present evidence that human leukocyte antigen-B-associated transcript 3 (Bat3), an important regulator involved in apoptosis, can interact with YWK-II/APLP2 and enhance its stability by reducing its ubiquitination and degradation by the ubiquitin-proteasome system. Co-expression of different Bat3 domain deletion constructs with YWK-II/APLP2 reveals that the proline-rich domain of Bat3 is required for its binding to YWK-II/APLP2. In addition, we find that the protein levels of YWK-II/APLP2 could be enhanced by nuclear export of Bat3 under apoptotic stimulation. We also find elevated levels of Bat3 and YWK-II/APLP2 in human colorectal cancer with a positive correlation between the two. Taken together, these results have revealed a previously undefined mechanism regulating cell apoptosis and suggest that aberrant enhancement of YWK-II/APLP2 by nuclear export of Bat3 may play a role in cancer development by inhibiting cell apoptosis.

Date: May. 28, 2012

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