Acetylation of the DNA Binding Domain Regulates Transcription-independent Apoptosis by p53*
AUTOR(ES)
Sykes, Stephen M.
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
The tumor suppressor p53 induces apo pto sis by altering the transcription of pro-apo pto tic targets in the nucleus and by a direct, nontranscriptional role at the mitochondria. Although the post-translational modifications regulating nuclear apo pto tic functions of p53 have been thoroughly characterized, little is known of how transcription-independent functions are controlled. We and others identified acetylation of the p53 DNA binding domain at lysine 120 as a critical event in apo pto sis induction. Although initial studies showed that Lys-120 acetylation plays a role in p53 function in the nucleus, we report here a role for Lys-120 acetylation in transcription-independent apo pto sis. We demonstrate that the Lys-120-acetylated isoform of p53 is enriched at mitochondria. The acetylation of Lys-120 does not appear to regulate the ability of p53 to interact with the pro-apo pto tic proteins BCL-XL and BAK. However, displacement of the inhibitory MCL-1 protein from BAK is compromised when Lys-120 acetylation is blocked. Functional studies show that mutation of Lys-120 to a nonacetylated residue, as occurs in human cancer, inhibits transcription-independent apo pto sis, and enforced acetylation of Lys-120 enhances transcription-independent apo pto sis. These data support a model whereby Lys-120 acetylation contributes to both the transcription-dependent and -independent apo pto tic pathways induced by p53.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2740446Documentos Relacionados
- Transcription-dependent and transcription-independent nucleosome disruption induced by dioxin.
- Transcription-independent DNA translocation of bacteriophage T7 DNA into Escherichia coli.
- Transcription-Independent RNA Polymerase II Dephosphorylation by the FCP1 Carboxy-Terminal Domain Phosphatase in Xenopus laevis Early Embryos
- Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding
- Transcription-independent phosphorylation of the RNA polymerase II C-terminal domain (CTD) involves ERK kinases (MEK1/2).