p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, including proliferating basal cells of epithelial layers in the epidermis, cervix, urothelium, and prostate. Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus corresponding to the transactivation domain of p53. We demonstrate that these truncated p63 variants can act as dominant-negative agents toward transactivation by p53 and p63, and we suggest the possibility of physiological interactions among members of the p53 family.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
A
A
Yang
M
M
Kaghad
Y
Y
Wang
E
E
Gillett
M D
MD
Fleming
V
V
Dötsch
N C
NC
Andrews
D
D
Caput
F
F
McKeon
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009115:Muridae; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins