DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis

Citation
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
Citations number
55
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
00219525 → ACNP
Volume
151
Issue
3
Year of publication
2000
Pages
495 - 505
Database
ISI
SICI code
0021-9525(20001030)151:3<495:DIAPGW>2.0.ZU;2-E
Abstract
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.