Dystrophin Dp71, a novel tumor suppressor?
Dystrophins belong to a group of proteins encoding by the Duchenne muscular dystrophy (DMD) gene. DMD gene generates full-length dystrophin (427 kDa) and different C-terminal truncated isoforms through alternative usage of internal promoters. Short isoforms are termed in accordance with their molecular mass as Dp140, Dp116, Dp71 and Dp40. Dystrophin Dp71, is ubiquitously expresses, with the exception of skeletal muscle, and is the predominant DMD gene product in nervous system. In addition, Dp71 undergoes alternative splicing of exons 71 and/or 78 to generate different splicing variants, being Dp71f (−71/−78) and Dp71d (−71/+78) the most studied isoforms. While deficiency of dystrophin causes muscle degeneration, absence of Dp71 has been implicated in cognitive impairment and abnormal retinal physiology, two well-defined non-muscular alterations of DMD patients, reviewed in (1). As dystrophin does, Dp71 associates with sarcoglycans, dystroglycans, syntrophins and dystrobrevin, to conform the plasma membrane-associated dystrophin associated protein complex. Such protein assembly provides stability to the plasma membrane and modulates cell signaling. Interestingly, Dp71 undergoes nuclear import trough recognition of an atypical nuclear localization signal by the importin α2/β1 system. Nuclear Dp71 in turn, is involved in the maintenance of nuclear architecture, via its interaction with nuclear envelope proteins, including emerin and lamins A/C and B1 (2). Thus, it appears that Dp71 is a multifunctional protein that interacts with different partners in both the cytoplasm and nucleus, which enables it to modulate a variety of cell functions.