FKBPs in chromatin modification and cancer

FK506-binding proteins (FKBPs) are intracellular receptors for FK506 and rapamycin, immunosuppressants that have recently been utilized as anticancer drugs. In the cytoplasm, FKBPs and these drugs modulate signal transduction pathways. However, recent reports reveal novel functions of FKBPs in the nucleus, which include regulation of transcription factors, histone chaperone activity, and modifications of chromatin structure. These activities are known to affect gene expression, DNA repair, and DNA replication. Therefore, elucidation of the nuclear functions of FKBPs will help researchers and clinicians better understand how immunosuppressants work as anticancer drugs, which might in turn lead to novel designs of cancer therapy.

► FKBPs regulate DNA-binding activities of transcription factors YY1 and IRF-4.
► FKBPs regulate the stability of transcription factors p53 and HIF1α.
► FKBPs (FKBP25, Fpr3, and Fpr4) might function as histone chaperones.
► FKBPs modify chromatin structure by interacting with HDACs and by PPIase activity.