We evaluated serologic response of 42 Middle East respiratory syndrome coronavirus (MERS-CoV)-infected patients according to 4 severity groups: asymptomatic infection (Group 0), symptomatic infection without pneumonia (Group 1), pneumonia without respiratory failure (Group 2), and pneumonia progressing to respiratory failure (Group 3). None of the Group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 100% in Group 0, 1, 2, 3, respectively; P = 0.001). Group 3 patients showed delayed increment of antibody titers during the fourth week, while Group 2 patients showed robust increment of antibody titer during the third week. Among patients having pneumonia, 75% of deceased patients did not show seroconversion by the third week, while 100% of the survived patients were seroconverted (P = 0.003).

β-catenin is a key signal transducer in the canonical WNT pathway and is negatively regulated by ubiquitin-dependent proteolysis. Through screening of various deubiquitinating enzymes (DUBs), we identified ubiquitin specific protease 4 (USP4) as a candidate for β-catenin-specific DUB. The effects of USP4 overexpression or knockdown suggested that USP4 positively controls the stability of β-catenin and enhances β-catenin-regulated transcription. Domain mapping results revealed that the C-terminal catalytic domain is responsible for β-catenin binding and nuclear transport. Examination of colon cancer tissues from patients revealed a correlation between elevated expression levels of USP4 and β-catenin. Consistent with this correlation, USP4 knockdown in HCT116, a colon cancer cell line, reduced invasion and migration activity. These observations indicate that USP4 acts as a positive regulator of the WNT/β-catenin pathway by deubiquitination and facilitates nuclear localization of β-catenin. Therefore, we propose that USP4 is a potential target for anti-cancer therapeutics.

Cdo activates Akt via indirect interaction with APPL1 during myoblast differentiation, and this complex likely mediates some of the promyogenic effect of cell–cell interaction. The promyogenic function of Cdo involves a coordinated activation of p38MAPK and Akt via interaction with scaffold proteins, JLP and Bnip-2 for p38MAPK and APPL1 for Akt.