Perp is required for tissue-specific cell survival during zebrafish development.
The tumor suppressor p53 has two alternative effects, causing either cell cycle arrest or apoptosis. These different effects are supposed to be mediated by the transcriptional activation of different target genes. perp, encoding a transmembrane protein of the Pmp22 family, is a transcriptional p53 target exclusively upregulated in apoptotic cells. However, its role during normal development had remained largely unclear. Here, we report the isolation and characterization of a zebrafish perp homolog. Upon overexpression in early zebrafish embryos, perp induces apoptosis. In addition, it contributes to p53-dependent and UV-induced cell death. However, during normal zebrafish development, perp displays a p53-independent and spatially restricted expression in specific cell types and tissues. Antisense-mediated loss of Perp function leads to increased apoptosis in perp-expressing cells of the developing skin and notochord. We conclude that, in contrast to its proapoptotic function in stressed cells, Perp plays an antiapoptotic role during normal zebrafish development to regulate tissue-specific cell survival.
Nowak
M
M
Max-Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Köster
C
C
Hammerschmidt
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000528:radiation effects; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D009672:Notochord / Q000196:embryology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000008:administration & dosage; D012867:Skin / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
D061945:Caspase Inhibitors; D008565:Membrane Proteins; C503830:Perp protein, zebrafish; D010750:Phosphoproteins; D012333:RNA, Messenger; C488641:Tp63 protein, zebrafish; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C477072:tp73 protein, zebrafish; D020169:Caspases