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2 edition of p53 oligomerization domain found in the catalog.

p53 oligomerization domain

Timothy Scott Davison

p53 oligomerization domain

sequence-structure relationships and the design and characterization of altered oligomeric states.

by Timothy Scott Davison

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Published .
Written in English


About the Edition

p53 is a homotetrameric, tumor suppressor protein involved in transcriptional control of genes that regulate cell proliferation and death. In order to investigate the role that oligomerization plays in this capacity, the malleability of the sequence-structure relationship as it pertains to the quaternary structure, stability and oligomeric status of p53 is examined. This is achieved through scrutinizing the impact of two cancer-causing germline mutations found within the oligomerization domain and the analysis of hydrophobic to hydrophilic, single and double point mutations at the dimer-dimer interface, culminating in the design and structural characterization of a dimeric form of p53 by NMR. These studies produced a set of biophysically characterized p53 mutants with altered oligomeric status including monomers, dimers and destabilized tetramers ideal for probing the dependence of p53 function on oligomeric status. Specifically, studies involving the two germline mutations indicate that even partial abrogation of p53 oligomerization is sufficient for accelerated tumour progression. The prospect of functional interactions amongst p53 family members, including the p53 homologs p63 and p73, via conserved oligomerization domains is also assessed. Evidence is presented to show that the oligomerization domains of p63 and p73 preferentially fold into stable homotetramers, can form weak heterotetramers, but do not hetero-oligomerize with p53.

The Physical Object
Pagination168 leaves.
Number of Pages168
ID Numbers
Open LibraryOL20339291M
ISBN 100612917673

  Adrenocortical carcinoma (ACC) is a rare pediatric malignancy. It occurs in excess among individuals with the Li-Fraumeni syndrome, which results primarily from germline mutations in the TP53 gene. Prior series exploring frequencies of germline TP53 mutation among children with ACC have been small, geographically limited, or subject to referral bias.. The functional Cited by: Currently, protein interaction of Homo sapiens nucleotide binding domain (NBD) of heat shock 70 kDa protein (PDB: 1HJO) with p53 motif remains to be elucidated. The NBD-p53 motif complex enhances the p53 stabilization, thereby increasing the tumor suppression activity in cancer treatment. Therefore, we identified the interaction between NBD and p53 using STRING Cited by: 4.

The correct regulation of the p53 response to stress is vital for its effective function. The study of the control of p53 has been enormously exciting and at the cutting edge of modern molecular technology, from detailed structural investigations of its folding, stability, and oligomerization (Joerger and Fersht), through to analysis of its. p53 protein The p53 protein prevents cells with damaged DNA from dividing or, when damage is too great, promotes cell death. The primary structure of the protein is the sequence of amino acids linked together in a polypeptide chain; groups of amino acids, called domains, have specific functions, such as the binding of DNA.

Human protein p53 is a 53KDa phosphoprotein encoded by a 20Kb-gene; it has an intricate structure which is closely related to its function. Wild-type P53 protein contains five major domains. The N-terminus of p53 is a transcription-activation domain (TAD), with a major one at residues and a minor one at residues (Venot et al., ).   The classical p53 C-terminal domain contains the main post-translational modification sites regulating p53 stability, such as the lysines residues ubiquitinated by Mdm2, an E3-ubiquitin ligase Cited by:


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P53 oligomerization domain by Timothy Scott Davison Download PDF EPUB FB2

To identify structural and oligomerization domains in p53, we have investigated the physical properties of purified segments of p The central, specific DNA-binding domain within murine amino acids 80 to and human amino acids 83 to behaves predominantly as monomers during analysis by sedimentation, gel filtration, and gel by:   Certain Human Cancer-derived p53 Mutations Occur in the Oligomerization Domain and Inhibit p53 Oligomerization and Acetylation—Cancer-prone germ line mutations that link to Li-Fraumeni syndrome have been shown to affect p53 tetramerization.

We analyzed two of these familial cancer mutations, LP and RC, for their effect on p53 Cited by: Tumor protein p53, also known as p53, cellular tumor antigen p53 (UniProt name), the Guardian of the Genome, phosphoprotein p53, tumor suppressor p53, antigen NY-CO, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice).

This homolog Aliases: TP53, BCC7, LFS1, P53, TRP53, tumor. These differences argue that wild-type p53 has a nonglobular shape. To identify structural and oligomerization domains in p53, we have investigated the physical properties of.

The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues – of human p53 crystallized in the space group P3 1 There is one biologically relevant tetrameric domain in the Cited by: A comparison of different lectins suggests that oligomerization may be achieved in very different ways (Kishore et p53 oligomerization domain book, ).

Instead of using collagen helices as an oligomerization domain, three-stranded coiled-coil domains or other linkers are employed in some endocytic receptors. Oligomerization by coiled-coil domainsCited by: p53 Domains: Structure, Oligomerization, andTransformation differences argue that wild-type p53 has a nonglobular shape.

DNA-binding domain within murine amino acids 80. occurred at the oligomeric domain of p However, the effect of such interactions on p53 oligomerization and function remained to be investigated. Here, we report that the interaction of RBEL1A and p53 suppressed p53 oligomer formation in unstressed cells and in cells exposed to DNA damage.

Furthermore, purified RBEL1A blockedCited by: 2. We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p We find that p53 has two autonomous DNA-binding regions. One domain, from amino acid toforms stable tetramers and binds DNA nonspecifically.

The biological significance, ff any, of this. The binding affinity of p53 to MDM2 fell when p53 contained the mutation LP or RC found in Li-Fraumeni patients. c-Abl binds directly to the C-terminal basic domain of p53, and this interaction requires a tetramer.

c-Abl may stabilize the tetrameric conformation, resulting in a more stable pDNA complex. IV) The oligomerization domain (, 4D) consists of a beta-strand, followed by an alpha-helix necessary for dimerization, as p53 is composed of a dimer of two dimers.

A nuclear export signal (NES) is localized in this oligomerization domain. p53 mutations found in cancers are missense mutations that are mostly located in the central DNA-binding domain, and more than 80% of p53 mutation studies have focused on residues between – [27].

In the p53 family, both p73 and p63 show considerable homology with p53 and have similar domain structures including an oligomerization do-File Size: 1MB.

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the NOD2 gene located on chromosome NOD2 plays an important role in the immune recognizes bacterial molecules Aliases: NOD2, ACUG, BLAU, CARD15, CD.

Tumor protein p53, hay còn gọi là p53 là một protein quan trọng nằm trong điều hòa chu kỳ tế bào - gọi là gen áp chế khối u p Khi có tổn thương ở DNA, p53 làm ngừng chu kỳ tế bào cho đến khi DNA bị tổn thương được sửa chữa hoặc p53 có thể làm cho tế bào chết theo lập trình (tiếng Anh en:apoptosis) nếu không còn Danh pháp: TP53, BCC7, LFS1, P53, TRP53.

acidic domain, passociating domain, – RING domain, zinc-finger domain, – genomic instability role, – history of study, – mouse studies, – p53 transactivation domain interactions, 61 MDR1 gain-of-function p53 mutations and multidrug resistance, mutant p53 target gene, 80, The p53 Mutation Handbook is a compilation of multiple analyses (NES) is localized in this oligomerization domain (Green).

V) The carboxy-terminus of p53 () contains 3 nuclear localization signals (NLS) and a non-specific DNA binding domain that binds to damaged DNA. This region is alsoFile Size: 2MB. Refers to a region in a protein that mediates the assembly of higher order protein complexes.

A major distinction between ODs and other protein-binding modules is that ODs are generally responsible for homotypic interactions or interactions between proteins in. The p53 tetramerization domain consists of a b-strand (Glu), a tight turn (Gly), and an α-helix (ArgGly) (Fig.

1 A). Approximately 50 % of human tumors carry inactivating mutations in the p53 gene. To date, 41 point mutations have been found in 22 positions among 31 residues of the tetramerization domain (Fig.

1 B).Author: Rui Kamada, Tomoko Terai, Takao Nomura, Yoshiro Chuman, Toshiaki Imagawa, Kazuyasu Sakaguchi. A long flexible region in each chain then connects to the DNA-binding domain PDB: 1olg- High-resolution structure of the oligomerization domain of p53 by multidimensional NMR Clore GM, Omichinski JG, Sakaguchi C-terminal basic domain: p53 contains a basic, lysine-rich domain which also functions as a negative regulatory domain.

P53 Network in Ovarian Cancer The cooperative action of p53 in BRCA1-driven tumorigenesis and in the induction of hereditary ovarian cancer is further strengthened by the phenotype of knock-out mice.

Brca1ï/ï mouse embryos are embryonic lethal at embryonic day ; if embryos are deleted. (A) Domain organization of p53 and sequence alignment of p53TAD with acidic TADs in VP16 and p p53 consists of transactivation domain (TAD), proline-rich domain (PR), DNA-binding domain (DBD), oligomerization domain (OD), and C-terminal domain (CTD).Cited by: 3.The structure of p63 seems to be more similar to the structure of p73 than to p p63 has a long transactivation domain (TA), a DNA binding domain (DBD) and an oligomerization domain (OD) that are all highly conserved with the corresponding domains in p53 and p The protein is composed of 15 exons and various isoforms of protein exist.We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p We find that p53 has two autonomous DNA-binding regions.

One domain, from amino acid toforms stable tetramers and binds DNA by: