Functional analysis of Cyclophilin B reveals a cell cycle dependent nucleolar pattern with a possible role in rDNA transcription

Cyclophilin B (CypB) belongs to the family of Cyclophilins, ubiquitously distributed proteins with confirmed functions in nucleus, cytoplasm and as intercellular communicator. CypB is able to combine these functions through the presence of a N-terminal nuclear localization signal (NLS) that becomes active after selective removal of the first 33 amino acids. Immunofluorescent staining in human dermal fibroblasts revealed that CypB expression follows a cell cycle dependent pattern with a particular preference for localization at the nucleoli. The fusion of different deletion mutants with GFP allowed reconstruction of the various described phenotypes found in literature. We found that CypB contains in fact a nucleolar localization signal that allows efficient relocation to the nucleoli in a cell cycle dependent manner. CypB revealed a high preference for the fibrillar centers (FC’s). In these FC’s CypB colocalized with factors involved in rDNA transcription, such as RNA-polymerase, Upstream binding factor-1 (UBF) and fibrillarin. This protein association was maintained after disruption of the nuclear architecture with adenosine analog DRB and became associated with cajal bodies. We propose that CypB interacts with these proteins and is involved in the rDNA transcription during the transcriptionally more active phases of the cell cycle. This work is supported by a BOF grant provided by University Gent, Belgiu