10-15-2014d2340 -https://mail.google.com/mail/u/0/#search/p53+isoforms/14913d85259ee60d { Dear Kurt, I am currently writing the first manuscript describing the characterisation of new mouse p53 isoforms (biological activities and biochemical activities of D157p53 and D157p53AS). You found the only publication where all mouse p53 isoforms are described in a diagram. You could look also at the work of Varda Rotter in 1986 and after where she described the mouse p53AS (splice variant similar to human p53beta). The p53AS is hyperactive compared to p53 (p53alpha) Heidi Scrable has studied D40p53 that she called p44 or DNp53. She has published several times on p44 (D40p53) Antony Braithwaite has generated a mutant D122p53 isoforms (overexpressing D122p53) Slater et al., Blood. 2011 May 12;117(19):5166-77. Wei et al, PNAS used Gerbil to show that Helicobacter Pylori promote gastric cancer by unbalancing p73/p53 isoforms (Wei et al., Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):E2543-50 Franck Toledo has generated mice deleted of the p53 splice variant (p53alpha and p53AS) Cell Rep. 2013 Jun 27;3(6):2046-58. He talked briefly about the KO p53AS mice that I generate with him. We have also generated the KO D157p53 mice. both mice develop pathologies that we are characterising. James Manfredi has generated mice that have lost part of the alpha domain but can still express p53AS (different from Toledo’s mice) Genes Dev. 2013 Sep 1;27(17):1868-85. I hope it helps. Please do not hesitate to contact me if you need further information Cheers Jc } -You found the only publication where all mouse p53 isoforms are described in a diagram. -Varda Rotter in 1986 and after where she described the mouse p53AS (splice variant similar to human p53beta). The p53AS is hyperactive compared to p53 (p53alpha) -Heidi Scrable has studied D40p53 that she called p44 or DNp53. She has published several times on p44 (D40p53) -Antony Braithwaite has generated a mutant D122p53 isoforms (overexpressing D122p53) Slater et al., Blood. 2011 May 12;117(19):5166-77. "C:\ativ6_storage\projects\cnio\DR\2014\10-16-2014d0920\HT Q-FISH Protocol from Aksinya 10-16-2014d0920.pdf" Official news about receiving CNIO Banco Santander Fellowship for 2 years and 30,400 to 34,200 Euros per year -https://mail.google.com/mail/u/0/#search/fellowships/1491457f770ba974 ----------- 10-16-2014d0930 Biological functions of p53 isoforms through evolution: lessons from animal and cellular models Cell Death and Differentiation 2011 UK and France paper J-C Bourdon paper With all of these different isoforms, I really wonder how many of them are legitimate isoforms with biological function, and how many of them are common mistakes committed by cells when trying to splice the RNA. It seems that many of the isoforms inhibit the function of the most common full-length alpha isoform. -q alternative promoters, splicing sites and translational initiation sites, that are conserved through evolution and within the TP53 homologues, TP63 and TP73. -q the importance of p53 isoforms in regulating the suppressive functions of p53 has only become evident in the last 10 years, s: how to overcome size limitations with gene therapy -q the deregulation of p53 isoform expression in human cancers is reviewed -q evaluation of the use of p53 isoform as biomarkers in human cancers. -q . 2 The ability of p53 to integrate signals implies the existence of multiple and subtle levels of regulation q However, with the generation of isoform- speci?c knockout mice, a subtle interplay between the N-terminal isoforms has recently emerged, with the dynamic expression of N-terminal p63 or p73 isoforms appearing critical for maintaining the normal sequence of cell develop- ment (from stem to committed progenitors and then differ- entiated cells). 19,20 -q p53 protein isoforms through conserved mechanisms. 6,7 The main and most abundant p53 isoform is the canonical p53 protein, also termed TAp53a, as it contains an entire TAD and the longest C-terminal domain -q G-quadruplex structures promote the correct splice-out of intron-2 -q Thus, it should be kept in mind that some cells or tumours considered as ‘p53-null’ because of the presence of frameshift or nonsense mutations, may retain the capacity to express one or several p53 isoforms. -q experiments demonstrate that the direct binding of p53 onto the p53REs results in an increased expression of both D133p53 mRNAs and the D133p53a protein -q The C-terminal spliced p53 forms, b and c -q These data support the notion that D40p53a inhibits basal p53 activities during cell- cycle progression. -q 3 D133p53a does not bind to consensus p53REs in vitro, consistent with its partial lack of the DNA- binding domain, and thus can also behave as a dominant mutant p53 protein. 3 -q these results are consistent with an oncogenic capacity of D133p53. -q The biological functions of the C-terminal p53 isoforms (i.e., p53b and p53g) remain poorly described and controversial. -q Thus, there is still debate on whether p53b or p53g exert their activities in an autonomous manner or through an interaction with p53 -q Overall, current experimental data on the biological roles of p53 isoforms are fragmented --It looks like we have a lot to learn -q insight into which of these functions are of physiolo- gical or pathological relevance may come from animal model studies -q The Drosophila p53 gene is activated by irradiation and exerts broad suppressive effects recapitulating those of the p53-family members, including regulation of apoptosis, aging, autophagy, differentiation and growth Mouse section -q Six p53 isoforms have been described in mice, resulting from combination of three N-terminal p53 isoforms with two different C-terminal isoforms -q In 2004, Maier et al. 65 described a transgenic mouse overexpressing MD41p53 (Table 1). When expressed in a p53-null background, this isoform did not induce any particular phenotype. However, when expressed in a p53-competent background, an increased dosage of MD41p53 led to reduced size, accelerated aging and a shorter lifespan associated with hypo-insulinemia and glucose insuf?ciency. -q A premature aging phenotype was also reported in a non- physiological knock-in p53 mouse model expressing a ‘MD122p53’ form, truncated for the ?rst 122 residues -q p53 D122p53/D122p53 mice showed pre- mature aging symptoms, such as balding and arthritis, similar to that observed in the p53 þ /m mice ( -q In addition, earlier tumour onset and shortened lifespan were observed in p53 þ /D122p53 mice as compared with p53 þ / mice -q mouse N-terminal p53 forms may operate as dominant oncogenes to promote cell proliferation and in?ammation Nice summary part { -q overall patterns of isoform expression are well-conserved throughout evolution -q Second, N-terminal isoforms have a major role as regulators of physiological processes related to development, aging, life- span and, possibly, carcinogenesis. --Is this completely accurate? Is an an absence of function a "major role"? Well the authors probably have thought about this. -q It should, however, be remem- bered that our current view of isoform activities remains fragmentary and that further studies are needed to better understand their roles and underlying mechanisms. } -q TP53 gene is highly polymorphic, with over 80% of known single-nucleotide polymorphisms (SNPs) located within introns or non-coding 50 and 30 sequences. -q carriers bearing A1A1 genotypes developed their ?rst cancer on average 20 years earlier than carriers with an A1A2 genotype -q owing to a widespread founder effect Table 2 Role of p53 isoforms in human cancers -q Given the role of N-terminal p53 forms as inhibitors of p53 transactivation, it can be expected that overexpression of certain isoforms may represent an alternative to a mutation in TP53 for inactivating p53 in cancers, as observed in some small clinical studies. 33,74,75 -q There is emerging evidence that p53 isoform expression is deregulated in human cancers -q The ?eld of ‘p53 isoforms’ is still in its infancy, but the increasing number of genetic, biochemical and clinical studies have clearly established that p53 isoforms are fundamental and important components of the p53 pathway -q characteriza- tion of the biochemical and biological activities of p53 isoforms will impact on the ?elds of cancer, embryo development and aging -q Further progress on this front will require the development of robust and standardized tools for the identi?cation and quanti?cation of p53, p63 and p73 protein isoform expression in experimental systems as well as in human tissues. There's a nice facts and open questions section at the end -q p53 isoforms in the p53 network --------- 10-16-2014d1214 routing number bbva spain -https://answers.yahoo.com/question/index?qid=20070419231109AASaQmG Código de banco or Número ABA sequences for mouse p53 isoforms 10-16-2014d1457 http://stackoverflow.com/questions/8490968/select-range-of-lines-in-notepad how to select a range in notepad++ -http://stackoverflow.com/questions/8490968/select-range-of-lines-in-notepad -Ctrl+G go to line x->Menu->Edit->Begin/End select->Ctrl+G go to line y->Menu->Edit->Begin/End select 1 to 157 exon1 86 to 88 "upstream in-frame stop codon" 158 to 1330 coding sequence 473 to 1015 is DNA binding domain 1118 to 1225 is p53 tetramerization motif 179 to 250 is p53 transactivation motif 677 to 685 and AG689 to 691 dimerization site 158 to 240 exon2 241 to 262 exon3 263 to 523 exon4 524 to 707 exon5 708 to 820 exon6 821 to 930 exon7 931 to 1067 exon8 1068 to 1141 exon9 1142 to 1248 exon10 1249 to 1772 exon11 1751 to 1756 poly A signal 1772 poly A site AE = isoform A exon UIS = upstream in-frame stop codon APAS = isoform A poly A signal ASTC = isoform A start codon ASC = A stop codon TAD = transactivation motif dim = dimerization motif mouse p53 region dna 10-15-2014d1518 "C:\ativ6_storage\projects\cnio\DR\2014\10-05-2014d2156\version 2\mouse p53 isoform A transcript 10-16-2014d1537.ape" Now for isoform b http://www.ncbi.nlm.nih.gov/nuccore/NM_001127233.1 P = total p53 promoter sequence from 4 -different databases (UT Dallas Promoter Database, Wistar Institute Promoter Database, Eukaryotic Promoter Database, and Riken Mammalian Promoter Enhancer Database) Approximately 6 isoforms have been identified in mice, but the isoform A is the full length form and is most common Marcel, Virginie, et al. "Biological functions of p53 isoforms through evolution: lessons from animal and cellular models." Cell Death & Differentiation 18.12 (2011): 1815-1824. 1-157 ex1 86-88 upstream in-frame stop codon 158-1303 cds 473-1015 p53 dna-binding domain 1118-1225 p53 tetramerization motif 179-250 p53 transactivation motif 863-988 DNA binding site 677-691 dimerization site 158-240 ex2; ch 10-16-2014d1747 241-262 ex3; ch 10-16-2014d1748 263-523 ex4; ch 10-17-2014d1117 524-707 ex5; ch 10-17-2014d1118 708-820 ex6; ch 10-17-2014d1118 821-930 ex7; ch 10-17-2014d1118 931-1067 ex8; ch 10-17-2014d1119 1068-1141 ex9; ch 10-17-2014d1119 1142-1248 ex10; ch 10-17-2014d1120 1249-1868 ex11; ch 10-17-2014d1122 1847-1852 polyA signal 1868 polyA site Isabel and Gema 5 young males and 10 young females ------------ 10-17-2014d1036 p53, p53AS, delta41p53, delta41p53As, delta157p53, and delta157p53AS -sequences of interest --Mus musculus transformation related protein 53 (Trp53), transcript variant 1, mRNA ---aka isoform a ---http://www.ncbi.nlm.nih.gov/nuccore/NM_011640.3 ---NM_011640.3 --Mus musculus transformation related protein 53 (Trp53), transcript variant 2, mRNA ---aka isoform b ---http://www.ncbi.nlm.nih.gov/nuccore/NM_001127233.1 ---NM_001127233.1 --PREDICTED: Mus musculus transformation related protein 53 (Trp53), transcript variant X2, mRNA ---aka isoform X2 ---http://www.ncbi.nlm.nih.gov/nuccore/XM_006533158.1 ---XM_006533158.1 --PREDICTED: Mus musculus transformation related protein 53 (Trp53), transcript variant X1, mRNA ---isoform X1 ---http://www.ncbi.nlm.nih.gov/nuccore/XM_006533157.1 ---XM_006533157.1 -Received EL Buffer --"C:\ativ6_storage\projects\cnio\DR\2014\10-17-2014d1108\EL Buffer 10-17-2014d1108.pdf" ---------- 10-17-2014d1145 X1 transcript 539-1711 cds 854-1396 DNA binding domain; ch 10-17-2014d1153 1499-1606 p53 tetramerization motif; ch 560-631 TAD; ch 1244-1273 and 1346-1369 DNA binding site; ch 1055-1066 and 1241-1255 zinc binding site; ch 1048-1072 dimerization site query transcript subject genomic dna regions for X1 AGCTACCTGAAGACCAAGAAGGGCCAGTCTACTTCCCGCCATAAAAAAACAATGGTCAAGAAAGTGGGGCCTGACTCAGACTGACTGCCTCTGCATCCCGTCCCCATCACCAGCCTCCCCCTCTCCTTGCTGTCTTATGACTTCAGGGCTGAGACACAATCCTCCCGGTCCCTTCTGCTGCCTTTTTTACCTTGTAGCTAGGGCTCAGCCCCCTCTCTGAGTAGTGGTTCCTGGCCCAAGTTGGGGAATAGGTTGATAGTTGTCAGGTCTCTGCTGGCCCAGCGAAATTCTATCCAGCCAGTTGTTGGACCCTGGCACCTACAATGAAATCTCACCCTACCCCACACCCTGTAAGATTCTATCTTGGGCCCTCATAGGGTCCATATCCTCCAGGGCCTACTTTCCTTCCATTCTGCAAAGCCTGTCTGCATTTATCCACCCCCCACCCTGTCTCCCTCTTTTTTTTTTTTTTACCCCTTTTTATATATCAATTTCCTATTTTACAATAAAATTTTGTTATCACTTA GCCGCTTCTCGACCCTGCTAGATGAAGAAAATCCAAGAAAAGCCTGAAGCACTAGCGGTGCTAGCCAGAAGTATTTGCCCTCGGGGCCCGACTCAGCCTCTTGGTCTGAAAGGCCCGCCGGCCCTGTTATTGTTTGGCTCCTTTACGTTTCTGCCGCTTGCAGGAGCATTTCCGGTTTCTTGTTTTCGGAGCAGATCACTGCTCGCCCGGCGACGGGGGAGTAGCGAAAGGGGAGAAATGGATTCTAGGCTGGTTCTGTGGTTTGAGGAGGAAAACTGCTGTCCTCGACATCTTATTTTTCTGGATTACTTGGTTATTGCTTTTGCAAAGGAGGAGGTGTTTATTTAAAAGAGTGCGCCGATAGGTCGTTTCTTCCTGCCGGAAAAGCAAATTACCGAGTATCCGGTTTTAGGGTGA GCCATCACCTCACTGCATGGACGATCTGTTGCTGCCCCAGGATGTTGAGGAGTTTTTTGAAGGCCCAAGTGAAGCCCTCCGAGTGTCAGGAGCTCCTGCAGCACAGGACCCTGTCACCGAGACCCCTGGGCCAGTGGCCCCTGCCCCAGCCACTCCATGGCCCCTGTCATCTTTTGTCCCTTCTCAAAAAACTTACCAGGGCAACTATGGCTTCCACCTGGGCTTCCTGCAGTCTGGGACAGCCAAGTCTGTTATGTGCACG GTACTCTCCTCCCCTCAATAAGCTATTCTGCCAGCTGGCGAAGACGTGCCCTGTGCAGTTGTGGGTCAGCGCCACACCTCCAGCTGGGAGCCGTGTCCGCGCCATGGCCATCTACAAGAAGTCACAGCACATGACGGAGGTCGTGAGACGCTGCCCCCACCATGAGCGCTGCTCCGATGGTGATGG AGTGGGAACCTTCTGGGACGGGACAGCTTTGAGGTTCGTGTTTGTGCCTGCCCTGGGAGAGACCGCCGTACAGAAGAAGAAAATTTCCGCAAAAAGGAAGTCCTTTGCCCTGAACTGCCCCCAGGGAGCGCAAAGAGAG GTTCTGTAGCTTCAGTTCATTGGGACCATCCTGGCTGTAGGTAGCGACTACAGTTAGGGGGCACCTAGCATTCAGGCCCTCATCCTCCTCCTTCCCAGCAGGGTGTCACGCTTCTCCGAAGACTGG GGCCTGGCTCCTCCCCAGCATCTTATCCGGGTGGAAGGAAATTTGTATCCCGAGTATCTGGAAGACAGGCAGACTTTTCGCCACAGCGTGGTGGTACCTTATGAGCCACCCGAGG CCCCAGGCCGGCTCTGAGTATACCACCATCCACTACAAGTACATGTGTAATAGCTCCTGCATGGGGGGCATGAACCGCCGACCTATCCTTACCATCATCACACTGGAAGACTCCAGGTAGGAA AGATCCGCGGGCGTAAACGCTTCGAGATGTTCCGGGAGCTGAATGAGGCCTTAGAGTTAAAGGATGCCCATGCTACAGAGGAGTCTGGAGACAGCAGGGCTCACTCCAG GATGACTGCCATGGAGGAGTCACAGTCGGATATCAGCCTCGAGCTCCCTCTGAGCCAGGAGACATTTTCAGGCTTATGGAAACT AGCGCTGCCCACCTGCACAAGCGCCTCTCCCCCGCAAAAGAAAAAACCACTTGATGGAGAGTATTTCACCCTCAAG program to automatically annotate DNA sequence maybe Blast2GO s: automatically create graphical annotations from genbank file -BioEdit -Sequin -ApE can do this -genoplotr -IGS Manatee no arrow /ApEinfo_graphicformat=arrow_data {{} {} 0} width 5 offset X2E mouse p53 genomic sequence with annotated introns and exons found here -http://p53.iarc.fr/TP53Sequence_NC_000017-9.aspx X2E I would like to know which sequence numbers each isoform is missing and what this corresponds to query mouse isoform X2 subject = genomic sequence 16478-17003; ch 12501-12762; ch 13493-13678; ch 14701-14839; ch 5520-5645; ch 13755-13869; ch 14265-14385; ch 15784-15892; ch 6183-6285; ch 12020-12103; ch 14917-14992; ch "C:\ativ6_storage\2014\10-18-2014d1118\com.cerience.reader.app-4.2.9-paid-d82c-www.apkhere.com.apk" -------- 10-18-2014d1251 -Reconstruction and analysis of cancer-specific gene regulatory networks from gene expression profiles --http://arxiv.org/ftp/arxiv/papers/1305/1305.5750.pdf -Integrative Gene Network Construction to Analyze Cancer Recurrence Using Semi-Supervised Learning --http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0086309 -Find subnetworks of differentially expressed genes --http://www.genomespace.org/support/guides/recipes/sections/find-subnetworks-of-differentially-expressed-genes -[Possible sources of data to compare healthy and disease or aged networks 09-26-2014d1648] ftp spaces online ftp sites online -iweb-ftp -hosting4less -drivepop (this might be the best one; as of 10-18-2014d1337, 1 TB for $15 per month) Recent work has also shown that natural selection tends to favor networks with sparse connectivity.[33] -Survival of the sparsest: robust gene networks are parsimonious --q "We show that when the costs of complexity are taken into account, that robustness implies a parsimonious network structure that is sparsely connected and not unnecessarily complex; and that selection will favor sparse networks when network topology is free to evolve." Some traits of complex adaptive systems 10-18-2014d1431 I owe Sun Valley medical clinic $154.00. I sent them an email asking how to pay this. office@sunvalleymedicalbilling.com -https://mail.google.com/mail/u/0/#search/bill+from+clinic/14916298bb6d46be The Continent -http://www.imdb.com/title/tt3896016/?ref_=fn_al_tt_1 7- 113