Anti-Ro/SSA antibodies are antinuclear antibodies most commonly found in 
patients with Sjögren's syndrome, a chronic autoimmune disease characterized by 
dryness of the eyes and mouth. The autoantibodies recognize a RING-finger 
protein, Ro52/SSA (52 kDa), whose function is still unknown. In this study, the 
ubiquitination of Ro52 was investigated. We found that Ro52 was strongly 
conjugated by a single molecule of ubiquitin in cells. Although the biological 
relevance of this mono-ubiquitination was not defined, the function of Ro52 
might be modified by the mono-ubiquitination. We also found that Ro52 was 
conjugated with poly-ubiquitin chain in cells (poly-ubiquitination), suggesting 
that Ro52 may be downregulated by the ubiquitin-proteasome pathway in vivo. 
Interestingly, sera from patients with Sjögren's syndrome showed heterogeneity 
in their reactivity to poly-ubiquitinated Ro52, probably because of their 
differing antigenic determinants. This heterogeneity of the reactivity might be 
associated with the varying clinical features found in patients with Sjögren's 
syndrome.