p63 and p73 are not required for the development and p53-dependent apoptosis of T cells.
The recent discoveries of p63 and p73, homologs of the tumor suppressor p53, raised the possibility of a network of these family members governing cell cycle arrest and apoptosis in response to stress. However, mice lacking p73 show no tendency for spontaneous tumors, and mutations in p63 or p73 are rare in human tumors, rendering any obligate role of these genes in cell death and tumor suppression unclear. In an effort to reconcile these incongruent data, we examined the genetic interactions between p53, p63, and p73 in well-established paradigms of p53-dependent and -independent T cell death using primary, genetically defined lymphocytes. Our findings challenge the generality of the notion that p63 and p73 are required for p53 function or for apoptosis in T cells.
Senoo
Makoto
M
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Manis
John P
JP
Alt
Frederick W
FW
McKeon
Frank
F
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C499308:Rag2 protein, mouse; C000606460:TP73 protein, human; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C064655:V(D)J recombination activating protein 2