Fa. Scholl et al., DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis, J CELL BIOL, 151(3), 2000, pp. 495-505
DRAL is a four and a half LIM domain protein identified because of its diff
erential expression between normal human myoblasts and the malignant counte
rparts, rhabdomyosarcoma cells. In the current study, we demonstrate that t
ranscription of the DRAL gene can be stimulated by p53, since transient exp
ression of functional p53 in rhabdomyosarcoma cells as well as stimulation
of endogenous p53 by ionizing radiation in wild-type cells enhances DRAL mR
NA levels. In support of these observations, five potential p53 target site
s could be identified in the promoter region of the human DRAL gene. To obt
ain insight into the possible functions of DRAL, ectopic expression experim
ents were performed. Interestingly, DRAL expression efficiently triggered a
poptosis in three cell lines of different origin to the extent that no cell
s could be generated that stably overexpressed this protein. However, trans
ient transfection experiments as well as immunofluorescence staining of the
endogenous protein allowed for the localization of DRAL in different cellu
lar compartments, namely cytoplasm, nucleus: focal contacts, as well as Z-d
iscs and to a lesser extent the M-bands in cardiac myofibrils. These data s
uggest that downregulation of DRAL might be involved in tumor development.
Furthermore, DRAL expression might be important for heart function.