F08-BCH361-L27

F08-BCH361-L27 - Lecture 27 Live or let die: The protection...

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Lecture 27 Live or let die: The protection from cancer and aging The cell response to the tumor supressor protein p53
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The life of most cells that acquire potentially malignant characteristics is rapidly terminated, leaving only rare incipient cancer cells in which defects in the apoptotic response allow survival and further malignant progression .
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Compared with many normal tissues, cancer cells are highly sensitized to apoptotic signals, and survive only because they have acquired lesions — such as loss of p53 — that prevent or impede cell death. The aim of the present research is to understand the complex mechanisms that regulate whether or not a cell dies in response to p53 — insights that will ultimately contribute to the development of therapeutic strategies to repair the apoptotic p53 response in cancers.
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p53 functions p53 seems to have evolved in higher organisms to prevent tumor development. It it is activated in response to several malignancy-associated stress signals, resulting in the inhibition of tumor-cell growth.
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(Vousden and Lu Nature 2002)
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(Chene et al. Nature 2003)
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Regulation of p53 function by MDM2 (Chene et al. Nature 2003)
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The gene of the P53 protein (Vousden and Lu Nature 2002)
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Ribbon diagram of p53 core domain bound to DNA. (Chou et al. Science 1994)
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Structure of the DNA binding domain of p53 in a complex with the DNA The p53 core domain structure consists of a beta sandwich that serves as a scaffold for two large loops (the L2 and L3 loops) and a loop-sheet-helix motif (H2 helix). The two loops bind a zinc atom, and together with the H2 helix form a continuous surface at one end of the beta sandwich. zink L2 L3 H2
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Structure of the DNA binding domain of p53 in a complex with the DNA The six most frequently mutated amino acids of p53 are highlighted in yellow R249 G 245 R 248 R 273 R 282 R 175 zink
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(Vousden and Lu Nature 2002)
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Frequency and distribution of p53 mutants proline rich MDM2 binding
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Crystal structure of a peptide from the aminoterminal transactivation domain of p53 that is bound to the amino-terminal domain of MDM2 .(Kuisse Science 1996)
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c | Structure of the p53 tetramerization domain.
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This note was uploaded on 09/30/2011 for the course BCH 361 taught by Professor Fromme during the Fall '08 term at ASU.

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F08-BCH361-L27 - Lecture 27 Live or let die: The protection...

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