Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer-2

<p><b>Copyright information:</b></p><p>Taken from "Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer"</p><p>http://www.biomedcentral.com/1471-2148/7/180</p><p>BMC Evolutionary Biology 2007;7():180-180.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2072957.</p><p></p>itions inferred by the program Treefinder with a WAG+Γ8 model. Numbers at internal nodes are corresponding to bootstrap support values, obtained in the analysis of 100 replicates using the same program and model of sequence evolution. Due to the dense species sampling within the mammals interesting aspects of mammalian evolution are becoming apparent. There are clear differences in the evolutionary rates among the different groups, indicated by the branch length of the rooted tree, this is especially true for the four Neoteleost fish. There is also an acceleration observed for the mouse-like rodents, with a striking exception represented by the sequence of the mole rat , which is despite the fact of being a rather small rodent even more slowly evolving than the related rabbit (, lagomorph). In fact the only sequences among the tetrapods (amphibians, reptilian and mammalian) that are more slowly evolving than the one from are from the urodeles (axolotl and newts). The primary sequence of salamander p53 is more closely related to the ancestral protein of tetrapod vertebrates than the p53 proteins of any other of the studied groups

Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer-1

<p><b>Copyright information:</b></p><p>Taken from "Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer"</p><p>http://www.biomedcentral.com/1471-2148/7/180</p><p>BMC Evolutionary Biology 2007;7():180-180.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2072957.</p><p></p>ivation Domain; DBD, DNA Binding Domain; NLS, Nuclear Localisation Signal; TET, tetramerisation domain; REG, Regulatory domain; Regions I-V, highly conserved regions. Lysine (K), serine (S) and threonine (T) residues implicated in post-translational modifications are indicated. The protein domains depicted in the diagrams are not to scale. (B) Sequences alignment of human and axolotl p53 proteins. The conserved regions I to V are highlighted and many changes between the axolotl and human sequence are identified (arrows). See table-2 for a complete list of changes associated with mutations in the human protein

Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer-0

<p><b>Copyright information:</b></p><p>Taken from "Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer"</p><p>http://www.biomedcentral.com/1471-2148/7/180</p><p>BMC Evolutionary Biology 2007;7():180-180.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2072957.</p><p></p>μM pifithrin-α, added freshly diluted everyday). Limbs in panels A-D were amputated distally in the middle of the zeugopod and limbs in panels E-G were amputated proximally through the middle of the stylopod (see dotted lines in panels A & E for amputation levels)

Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer-3

<p><b>Copyright information:</b></p><p>Taken from "Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer"</p><p>http://www.biomedcentral.com/1471-2148/7/180</p><p>BMC Evolutionary Biology 2007;7():180-180.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2072957.</p><p></p>ciferase activities were significantly different from non-p53 controls (at least p < 0.05, data not shown). Error bar ± s.e.m. human and axolotl p53 induced luciferase expression were significantly different with the Hdm2 promoter (p < 0.01). Each assay was performed in triplicate at least 3 separate times

Mutant lamin A links prophase to a p53 independent senescence program

<p>Expression of oncogenes or short telomeres can trigger an anticancer response known as cellular senescence activating the p53 and RB tumor suppressor pathways. This mechanism is switched off in most tumor cells by mutations in p53 and RB signaling pathways. Surprisingly, p53 disabled tumor cells could be forced into senescence by expression of a mutant allele of the nuclear envelope protein lamin A. The pro-senescence lamin A mutant contains a deletion in the sequence required for processing by the protease ZMPSTE24 leading to accumulation of farnesylated lamin A in the nuclear envelope. In addition, the serine at position 22, a target for CDK1-dependent phosphorylation, was mutated to alanine, preventing CDK1-catalyzed nuclear envelope disassembly. The accumulation of this mutant lamin A compromised prophase to prometaphase transition leading to invaginations of the nuclear lamina, nuclear fragmentation and impaired chromosome condensation. Cells exited this impaired mitosis without cytokinesis and re-replicated their DNA ultimately arresting in interphase as polyploid cells with features of cellular senescence including increased expression of inflammatory gene products and a significant reduction of tumorigenicity <i>in vivo</i>.</p

Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer-4

<p><b>Copyright information:</b></p><p>Taken from "Urodele p53 tolerates amino acid changes found in p53 variants linked to human cancer"</p><p>http://www.biomedcentral.com/1471-2148/7/180</p><p>BMC Evolutionary Biology 2007;7():180-180.</p><p>Published online 28 Sep 2007</p><p>PMCID:PMC2072957.</p><p></p>ed with MNNG. (B) RT-PCR analysis of p53 target gene, Gadd45 (a p53 target gene cloned in axolotl [57, 58]), in control treated axolotl AL1 cells, cells exposed to UV (6h post-irradiation) and cells exposed to UV & treated with pifithrin-α. Both Gapdh and Ef1α were used as controls to demonstrate that the effects of UV and UV plus pifithrin-α were specific for Gadd45. (D-E) Western blot analysis of total p53 protein (CM5 antibody) on AL1 cells exposed to UV or treated with MNNG

Additional file 2: of Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects

Confirmation of DTNA deletion in the patient using quantitative real-time PCR analysis (qPCR). Description of data: qPCR data revealed one copy of the DTNA gene (18q12.1) in a patient DNA sample as compared to two copies of the gene in a normal control DNA sample. The data was normalized against GAPDH gene using the comparative ΔΔCt method. RQ (relative quantity) value is presented along the vertical axis. Each reaction was reproduced (repeated) in triplicate for both DNA samples (patient and control) and both genes (DTNA and GAPDH). The series of four ten-fold dilutions were included into analysis with the starting amount of DNA ~ 1 ng. The results obtained for one of the dilutions are depicted in the figure; for the rest dilutions, the ratio of quantity values between test and control samples was the same. (PNG 8 kb