From cell death to viral replication: the diverse functions of the membrane-associated FKBP38

FKBP38 is in many ways an exceptional member of the FK506-binding proteins. The calmodulin-regulated activity of FKBP38 for instance is unique within this protein family. The activated FKBP38 participates in apoptosis signaling by inhibiting the anti-apoptotic Bcl-2. Beyond this role in programmed cell death, FKBP38 seems to be involved in very different cellular processes that do not necessarily depend on the FKBP domain. These functions involve regulation of the kinase mTOR, regulation of neural tube formation, regulation of cellular hypoxia response, but also Hepatitis C virus replication. Pharmacological targeting of FKBP38 might therefore prove a successful strategy for intervention in different FKBP38-dependent processes, including programmed cell death in cancer or neurodegenerative diseases.

► Structural insights suggest origin for the unusual functional properties of FKBP38.
► FKBP38 activation by calmodulin regulates Bcl-2 in neuronal apoptosis.
► FKBP38 controls mTOR activity, neural tube formation, and cellular hypoxia response.