title: DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis.
abstract: 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.
authors.affiliation: Division of Clinical Chemistry & Biochemistry, Department of Pediatrics, University of Zurich, 8032 Zurich, Switzerland.
authors.forename: F A
authors.initials: FA
authors.lastname: Scholl
authors.forename: P
authors.initials: P
authors.lastname: McLoughlin
authors.forename: E
authors.initials: E
authors.lastname: Ehler
authors.forename: C
authors.initials: C
authors.lastname: de Giovanni
authors.forename: B W
authors.initials: BW
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000528:radiation effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects
chemical_list: C105987:FHL2 protein, human; C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D020169:Caspases