Molecular structure of the p63 tumour suppressor and its complex with DNA.

Abstract

p63 transcription factor, the ancestral homolog of the p53 tumor suppressor, is crucial for genetic control of human reproduction. Lack of p63 activity results in severe developmental defects and loss of tumour and metastasis suppression.
We aim to analyse the structure-function relationship of the p63, alone and in complex with its specific DNA target. Revealing the architecture of p63 and the p63-DNA complex would provide us with molecular blueprint for the central tumour suppressor family and its structural and functional evolution that has led to a molecular fold with diversity of function.





References:
[1]

Moll UM, Slade N. (2004) p63 and p73: roles in development and tumor formation. Mol Cancer Res. 2(7):371-86

[2]

Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. (2011) The p53 family: guardians of maternal reproduction. Nature Rev Mol Cell Biol. 12(4):259-65.

[3]

Amelio I, Grespi F, Annicchiarico-Petruzzelli M, Melino G. (2012) p63 the guardian of human reproduction. Cell Cycle. 11(24):4545-51.

[4]

Deutsch GB, et al., (2011) DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer. Cell. 144(4):566-76

[5]

Aramayo R, Sherman MB, Brownless K, Lurz R, Okorokov AL, Orlova EV. (2011) Quaternary structure of the specific p53-DNA complex reveals the mechanism of p53 mutant dominance. Nucleic Acids Res. 39(20):8960-71.


Biological Areas:

Cell Biology
Structural Biology

BBSRC Area:

Molecules, cells and industrial biotechnology