PRESERVED DIAPHANOUS RELATED FORMIN AUTOREGULATORY DOMAIN

摘要

The iDiaphanous/i-related formins (DRFs) constitute a subclass of FH proteins known for their ability to bind activated Rho subfamily of small GTP-binding proteins which link FH proteins to cellular signalling pathways. The present inventor has identified a new homology domain unique to the DRFs that termed the DRF-autoregulatory domain (DAD) in the extreme Cterminus. DAD is involved in intramolecular binding with the GTPase binding domain (GBD) of the DRFs. Disclosed herein are compositions and methods that can disrupt this binding, and cause changes in cells including actin polymerization and/or stabilization of actin fibers resulting in growth inhibition or cell death by apoptosis. A preferred composition is peptide or polypeptide of no more than about 130 amino acids comprising the DAD peptide having the amino acid sequence [GA]-[VA]-M-D-x-L-L-E-x-L-[KRQ]-x-[GA]-[SGA]-[AP] (wherein amino acids within a set of brackets are interchangeable and x means any amino acid). Fusion proteins comprising DAD are also disclosed as are nucleic acids and expression vectors encoding these peptides and proteins.