TY  - JOUR
A1  - Deutsch, Gregor
A1  - Zielonka, Elisabeth M.
A1  - Coutandin, Daniel
A1  - Weber, Tobias Alexander
A1  - Schäfer, Birgit
A1  - Hannewald, Jens
A1  - Luh, Laura Martina
A1  - Durst, Florian
A1  - Ibrahim, Mohamed
A1  - Hoffmann, Jan
A1  - Niesen, Frank H.
A1  - Sentürk, Aycan
A1  - Kunkel, Hana
A1  - Brutschy, Bernd
A1  - Schleiff, Enrico
A1  - Knapp, Stefan
A1  - Acker-Palmer, Amparo
A1  - Grez, Manuel
A1  - McKeon, Frank
A1  - Dötsch, Volker
T1  - DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer
T2  - Cell
N2  - TAp63a, 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 TAp63a’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 TAp63a inhibition remains unknown. Here, we show that TAp63a is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with ~20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63a 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 TAp63a is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/36932
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-369328
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087504
SN  - 0092-8674
SN  - 1097-4172
N1  - Open access under CC BY license.
VL  - 144
IS  - 4
SP  - 566
EP  - 576
PB  - Cell Press
CY  - Cambridge, Mass
ER  -