Differential regulation of transcription and induction of programmed cell death by human p53-family members p63 and p73.
The p53 tumor suppressor acts as a transcription factor and has a central function in controlling apoptosis. With p63 and p73 two genes coding for proteins homologous to p53 have been identified. We describe the properties of seven human p63 and p73 proteins as transcriptional activators of p21WAF1/CIP1 expression and apoptotic inducers in direct comparison to p53 in the same assay systems employing DLD-1-tet-off colon cells. Programmed cell death is detected in cells expressing high levels of p53 and p73alpha. Cells overexpressing TAp63alpha, TAp63gamma, TA*p63alpha, TA*p63gamma, DeltaNp63alpha, and DeltaNp63gamma display low or no detectable apoptosis.
Dietz
Sebastian
S
Medizinische Klinik und Poliklinik II, Max Bürger Forschungszentrum, Universität Leipzig, Johannisallee 30, D-04103, Leipzig, Germany.
Rother
Karen
K
Bamberger
Casimir
C
Schmale
Hartwig
H
Mössner
Joachim
J
Engeland
Kurt
K
D000230:Adenocarcinoma / Q000378:metabolism*; D017398:Alternative Splicing; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C081876:CKAP4 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C115051:TP63 protein, human; C000606460:TP73 protein, human; C108581:Tp63 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020169:Caspases