DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer.
Cell
; 144(4): 566-76, 2011 Feb 18.
Article
en En
| MEDLINE
| ID: mdl-21335238
ABSTRACT
TAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Remarkably, already undamaged oocytes express high levels of the protein, suggesting that TAp63α's activity is under tight control of an inhibitory mechanism. Biochemical studies have proposed that inhibition requires the C-terminal transactivation inhibitory domain. However, the structural mechanism of TAp63α inhibition remains unknown. Here, we show that TAp63α is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with â¼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. Furthermore, we show that a helix in the oligomerization domain of p63 is crucial for tetramer stabilization and competes with the transactivation domain for the same binding site. Our results demonstrate how TAp63α is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oocitos
/
Fosfoproteínas
/
Transactivadores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania