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Published online 30 October 2000. doi:10.1083/jcb.151.3.495
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© The Rockefeller University Press, 0021-9525/2000//495 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 495-506

Original Article

Dral Is a P53-Responsive Gene Whose Four and a Half Lim Domain Protein Product Induces Apoptosis



Florence A. Scholla, Patricia McLoughlina, Elisabeth Ehlerb, Carla de Giovannic, and Beat W. Schäfera

a Division of Clinical Chemistry & Biochemistry, Department of Pediatrics, University of Zurich, 8032 Zurich, Switzerland
b Institute of Cell Biology, ETH Hoenggerberg, 8093 Zurich, Switzerland
c Institute of Cancer Research, University of Bologna, 40126 Bologna, Italy
Division of Clinical Chemistry & Biochemistry, Dept. of Pediatrics, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland.41-1-266 71 6941-1-266 75 53

DRAL is a four and a half LIM domain protein identified because of its differential expression between normal human myoblasts and the malignant counterparts, rhabdomyosarcoma cells. In the current study, we demonstrate that transcription of the DRAL gene can be stimulated by p53, since transient expression of functional p53 in rhabdomyosarcoma cells as well as stimulation of endogenous p53 by ionizing radiation in wild-type cells enhances DRAL mRNA levels. In support of these observations, five potential p53 target sites could be identified in the promoter region of the human DRAL gene. To obtain insight into the possible functions of DRAL, ectopic expression experiments were performed. Interestingly, DRAL expression efficiently triggered apoptosis in three cell lines of different origin to the extent that no cells could be generated that stably overexpressed this protein. However, transient transfection experiments as well as immunofluorescence staining of the endogenous protein allowed for the localization of DRAL in different cellular compartments, namely cytoplasm, nucleus, focal contacts, as well as Z-discs and to a lesser extent the M-bands in cardiac myofibrils. These data suggest that downregulation of DRAL might be involved in tumor development. Furthermore, DRAL expression might be important for heart function.

Key Words: LIM domain protein • transcriptional regulation • p53 • apoptosis • subcellular localization

© 2000 The Rockefeller University Press

Abbreviations used in this paper: BAP, bacterial alkaline phosphatase; DRAL, down-regulated in rhabdomyosarcoma LIM protein; DRAL-CF, COOH-terminally FLAG-tagged DRAL; DRAL-NF, NH2-terminally FLAG-tagged DRAL; FHL, four and a half LIM domain; IR, ionizing radiation; MEF-2, myocyte enhancer binding factor 2; RMS, rhabdomyosarcoma.


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