| Structural highlights
Function
CEP1_CAEEL Transcriptional activator that binds the same DNA consensus sequence as p53. Has a role in normal development to ensure proper meiotic chromosome segregation. Promotes apoptosis under conditions of cellular and genotoxic stress in response to DNA damage, hypoxia, or starvation. However, not required for DNA repair in response to UV-C or to regulate cell-cycle progression. Required for induction of ced-13 in response to DNA damage. Regulates germline proliferation by activating phg-1.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
The DNA binding domains of human p53 and Cep-1, its C. elegans ortholog, recognize essentially identical DNA sequences despite poor sequence similarity. We solved the three-dimensional structure of the Cep-1 DNA binding domain in the absence of DNA and compared it to that of human p53. The two domains have similar overall folds. However, three loops, involved in DNA and Zn binding in human p53, contain small alpha helices in Cep-1. The alpha helix in loop L3 of Cep-1 orients the side chains of two conserved arginines toward DNA; in human p53, both arginines are mutation hotspots, but only one contacts DNA. The alpha helix in loop L1 of Cep-1 repositions the entire loop, making it unlikely for residues of this loop to contact bases in the major groove of DNA, as occurs in human p53. Thus, during evolution there have been considerable changes in the structure of the p53 DNA binding domain.
Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog Cep-1.,Huyen Y, Jeffrey PD, Derry WB, Rothman JH, Pavletich NP, Stavridi ES, Halazonetis TD Structure. 2004 Jul;12(7):1237-43. PMID:15242600[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schumacher B, Hofmann K, Boulton S, Gartner A. The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr Biol. 2001 Oct 30;11(21):1722-7. PMID:11696333
- ↑ Derry WB, Putzke AP, Rothman JH. Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science. 2001 Oct 19;294(5542):591-5. Epub 2001 Sep 13. PMID:11557844 doi:http://dx.doi.org/10.1126/science.1065486
- ↑ Hofmann ER, Milstein S, Boulton SJ, Ye M, Hofmann JJ, Stergiou L, Gartner A, Vidal M, Hengartner MO. Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis. Curr Biol. 2002 Nov 19;12(22):1908-18. PMID:12445383
- ↑ Deng X, Hofmann ER, Villanueva A, Hobert O, Capodieci P, Veach DR, Yin X, Campodonico L, Glekas A, Cordon-Cardo C, Clarkson B, Bornmann WG, Fuks Z, Hengartner MO, Kolesnick R. Caenorhabditis elegans ABL-1 antagonizes p53-mediated germline apoptosis after ionizing irradiation. Nat Genet. 2004 Aug;36(8):906-12. Epub 2004 Jul 25. PMID:15273685 doi:http://dx.doi.org/10.1038/ng1396
- ↑ Schumacher B, Hanazawa M, Lee MH, Nayak S, Volkmann K, Hofmann ER, Hengartner M, Schedl T, Gartner A. Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell. 2005 Feb 11;120(3):357-68. PMID:15707894 doi:http://dx.doi.org/10.1016/j.cell.2004.12.009
- ↑ Schumacher B, Schertel C, Wittenburg N, Tuck S, Mitani S, Gartner A, Conradt B, Shaham S. C. elegans ced-13 can promote apoptosis and is induced in response to DNA damage. Cell Death Differ. 2005 Feb;12(2):153-61. PMID:15605074 doi:http://dx.doi.org/10.1038/sj.cdd.4401539
- ↑ Garcia-Muse T, Boulton SJ. Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans. EMBO J. 2005 Dec 21;24(24):4345-55. Epub 2005 Dec 1. PMID:16319925 doi:http://dx.doi.org/7600896
- ↑ Quevedo C, Kaplan DR, Derry WB. AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. Curr Biol. 2007 Feb 6;17(3):286-92. PMID:17276923 doi:http://dx.doi.org/10.1016/j.cub.2006.12.038
- ↑ Derry WB, Bierings R, van Iersel M, Satkunendran T, Reinke V, Rothman JH. Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network. Cell Death Differ. 2007 Apr;14(4):662-70. Epub 2006 Dec 22. PMID:17186023 doi:http://dx.doi.org/10.1038/sj.cdd.4402075
- ↑ Stergiou L, Doukoumetzidis K, Sendoel A, Hengartner MO. The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans. Cell Death Differ. 2007 Jun;14(6):1129-38. Epub 2007 Mar 9. PMID:17347667 doi:http://dx.doi.org/10.1038/sj.cdd.4402115
- ↑ Arum O, Johnson TE. Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. J Gerontol A Biol Sci Med Sci. 2007 Sep;62(9):951-9. PMID:17895432
- ↑ Greiss S, Schumacher B, Grandien K, Rothblatt J, Gartner A. Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family. BMC Genomics. 2008 Jul 15;9:334. doi: 10.1186/1471-2164-9-334. PMID:18627611 doi:http://dx.doi.org/10.1186/1471-2164-9-334
- ↑ Masse I, Molin L, Mouchiroud L, Vanhems P, Palladino F, Billaud M, Solari F. A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. PLoS One. 2008 Oct 6;3(10):e3354. doi: 10.1371/journal.pone.0003354. PMID:18836529 doi:http://dx.doi.org/10.1371/journal.pone.0003354
- ↑ Luo J, Shah S, Riabowol K, Mains PE. The Caenorhabditis elegans ing-3 gene regulates ionizing radiation-induced germ-cell apoptosis in a p53-associated pathway. Genetics. 2009 Feb;181(2):473-82. Epub 2008 Nov 17. PMID:19015549 doi:http://dx.doi.org/genetics.107.080515
- ↑ Huyen Y, Jeffrey PD, Derry WB, Rothman JH, Pavletich NP, Stavridi ES, Halazonetis TD. Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog Cep-1. Structure. 2004 Jul;12(7):1237-43. PMID:15242600 doi:10.1016/j.str.2004.05.007
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