期刊
CELL DEATH AND DIFFERENTIATION
卷 16, 期 12, 页码 1582-1589出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2009.139
关键词
p73; p63; p53 family; heterooligomerization; tetramerization; transcriptional activity
资金
- Deutsche Forschungsgemeinschaft [DO 545/2-1]
- EU [LSHB-CT-019067]
- Centre for Biomolecular Magnetic Resonance at the University of Frankfurt (BMRZ)
- Cluster of Excellence Frankfurt
- Volkswagen Foundation
- Canadian Institutes for Health Research [1097737]
- Canadian Foundation for Innovation
- Genome Canada through the Ontario Genomics Institute
- GlaxoSmithKline
- Karolinska Institutet
- Knut and Alice Wallenberg Foundation
- Ontario Innovation Trust
- Ontario Ministry for Research and Innovation
- Merck Co., Inc.
- Novartis Research Foundation
- Swedish Agency for Innovation Systems
- Swedish Foundation for Strategic Research
- Wellcome Trust
p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain ( OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family. Cell Death and Differentiation (2009) 16, 1582-1589; doi: 10.1038/cdd.2009.139; published online 18 September 2009
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