| Structural highlights
Function
[P73_HUMAN] Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.[1] [2] [3]
Publication Abstract from PubMed
Tumor suppressors p53, p63 and p73 comprise a family of stress-responsive transcription factors with distinct functions in development and tumor suppression. Most human cancers lose p53 function, yet all three proteins are capable of inducing apoptosis or cellular senescence. Mechanisms are therefore under investigation to activate p73-dependent apoptosis in p53-deficient cancer cells. Significantly, the DNA-binding domain (DBD) of p73 escapes viral oncoproteins and displays an enhanced thermal stability. To further understand the variant features of p73, we solved the high-resolution crystal structure of the p73 DBD as well as its complex with the ankyrin repeat and SH3 domains of the pro-apoptotic factor ASPP2. The p73 structure exhibits the same conserved architecture as p53 but displays a divergent L2 loop, a known site of protein-protein interaction. The loop in p73 is changed by a two-residue insertion that also induces repacking around the site of the p53 mutational hotspot R175. Importantly, the binding of ASPP2 is preserved by conformational changes in both the ankyrin repeat and SH3 domains. These results further highlight the structural variation that impacts p53 family interactions within the p53 interactome.
Structural Basis for ASPP2 Recognition by the Tumor Suppressor p73.,Canning P, von Delft F, Bullock AN J Mol Biol. 2012 Aug 20. pii: S0022-2836(12)00648-1. doi:, 10.1016/j.jmb.2012.08.005. PMID:22917970[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grob TJ, Novak U, Maisse C, Barcaroli D, Luthi AU, Pirnia F, Hugli B, Graber HU, De Laurenzi V, Fey MF, Melino G, Tobler A. Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53. Cell Death Differ. 2001 Dec;8(12):1213-23. PMID:11753569 doi:10.1038/sj.cdd.4400962
- ↑ Kaelin WG Jr. The emerging p53 gene family. J Natl Cancer Inst. 1999 Apr 7;91(7):594-8. PMID:10203277
- ↑ Koida N, Ozaki T, Yamamoto H, Ono S, Koda T, Ando K, Okoshi R, Kamijo T, Omura K, Nakagawara A. Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis through physical interaction and phosphorylation. J Biol Chem. 2008 Mar 28;283(13):8555-63. doi: 10.1074/jbc.M710608200. Epub 2008 , Jan 3. PMID:18174154 doi:10.1074/jbc.M710608200
- ↑ Canning P, von Delft F, Bullock AN. Structural Basis for ASPP2 Recognition by the Tumor Suppressor p73. J Mol Biol. 2012 Aug 20. pii: S0022-2836(12)00648-1. doi:, 10.1016/j.jmb.2012.08.005. PMID:22917970 doi:http://dx.doi.org/10.1016/j.jmb.2012.08.005
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