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Structure-function relationship of p53 tumour suppressor protein

Structure-function relationship of p53 tumour suppressor protein
p53抑癌蛋白的结构与功能关系
批准号:
BB/E021042/1
负责人:
Elena Orlova
金额:
$44.8万
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2008
资助国家:
英国
项目状态:
已结题
起止时间:
2008 至 --

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中文摘要
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英文摘要
Tissue cells of multicellular organisms such as the human body function in a highly coordinated manner in order to prevent the development of any undesirable trends within a tissue or an organ. Environmental pressures and exposure to various genotoxic agents keeps our cells under the constant threat of mutations which can induce the development of cancer. Naturally our cells have developed multiple defense mechanisms to eliminate such mutated cells from healthy tissue and this task is initiated and performed by a number of proteins called tumour suppressors. p53 transcription factor is one such protein and has been termed the 'guardian of genome'. p53 is involved in quality control of our chromosomal DNAand its importance is highlighted by the fact that more than 50% of human cancers are associated with mutations in the p53 gene. A substantial wealth of knowledge has accumulated due to intensive biomedical and biochemical studies of p53's action but the underlying molecular mechanisms of its participation and response to DNA damage are still unclear. Understanding the structure-function relationship of this crucial molecule would require capturing a series of snapshots of the molecule in its different states and in complex with DNA. The natural diversity of the length of inner spacer in p53 response elements implies that study of p53-DNA interactions would elucidate the general mechanisms of transcription factors and other DNA-binding proteins. The visualisation of conformational changes within the p53 molecule will reveal the mechanism of its functioning that will be further explored experimentally. The first structure of the full length p53 gave us the launching platform for further analysis of its complexes with DNA and of cancer-relevant p53 mutants. In this project we will analyse the p53 molecules in a physiological environment using the state-of-art electron microscopy facilities in Birkbeck College. Image analysis and docking of known atomic structures of domains will allow analysis of different conformations of p53.
期刊论文(6)
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DOI: 10.1093/nar/gkw215
发表时间: 2016-07-27
期刊: Nucleic acids research
影响因子: 14.9
作者: [Kearns S, Lurz R, Orlova EV, Okorokov AL]
通讯作者: Okorokov AL
DOI: 10.15252/embj.201796629
发表时间: 2017-10-16
期刊: The EMBO journal
影响因子: --
作者: [Redzej A, Ukleja M, Connery S, Trokter M, Felisberto-Rodrigues C, Cryar A, Thalassinos K, Hayward RD, Orlova EV, Waksman G]
通讯作者: Waksman G
DOI: 10.1021/cr100353t
发表时间: 2011-12-14
期刊: CHEMICAL REVIEWS
影响因子: 62.1
作者: [Orlova, E. V., Saibil, H. R.]
通讯作者: Saibil, H. R.
DOI: 10.1093/nar/gkr386
发表时间: 2011-11-01
期刊: Nucleic acids research
影响因子: 14.9
作者: [Aramayo R, Sherman MB, Brownless K, Lurz R, Okorokov AL, Orlova EV]
通讯作者: Orlova EV
Structure and biochemical mechanism of DNA replication initiation machines
  • 批准号:
    BB/R002622/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $44.33万
  • 财政年份:
    2018
  • 负责人:
    Elena Orlova
  • 依托单位:
Structure of origin DNA melting and unwinding complexes of a viral replication protein
  • 批准号:
    BB/J006920/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $40.17万
  • 财政年份:
    2013
  • 负责人:
    Elena Orlova
  • 依托单位:
Structure-function analysis of Type IV secretion systems by cryo-electron microscopy
  • 批准号:
    MR/K012401/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $84.64万
  • 财政年份:
    2013
  • 负责人:
    Elena Orlova
  • 依托单位:
Structural basis of SPP1 bacteriophage infectivity
  • 批准号:
    BB/F012705/1
  • 项目类别:
    Research Grant
  • 资助金额:
    $42.17万
  • 财政年份:
    2008
  • 负责人:
    Elena Orlova
  • 依托单位:
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  • 项目类别:
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