Structural highlights
Function
P53_DANRE Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of bax and fas antigen expression, or by repression of Bcl-2 expression.[1] [2]
Publication Abstract from PubMed
The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome.
Tracing the Evolution of the p53 Tetramerization Domain.,Joerger AC, Wilcken R, Andreeva A Structure. 2014 Sep 2;22(9):1301-10. doi: 10.1016/j.str.2014.07.010. PMID:25185827[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Langheinrich U, Hennen E, Stott G, Vacun G. Zebrafish as a model organism for the identification and characterization of drugs and genes affecting p53 signaling. Curr Biol. 2002 Dec 10;12(23):2023-8. PMID:12477391
- ↑ Berghmans S, Murphey RD, Wienholds E, Neuberg D, Kutok JL, Fletcher CD, Morris JP, Liu TX, Schulte-Merker S, Kanki JP, Plasterk R, Zon LI, Look AT. tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):407-12. Epub 2005 Jan 3. PMID:15630097 doi:http://dx.doi.org/10.1073/pnas.0406252102
- ↑ Joerger AC, Wilcken R, Andreeva A. Tracing the Evolution of the p53 Tetramerization Domain. Structure. 2014 Sep 2;22(9):1301-10. doi: 10.1016/j.str.2014.07.010. PMID:25185827 doi:http://dx.doi.org/10.1016/j.str.2014.07.010
