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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-10
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pubmed:abstractText |
Upon DNA damage, a complex called the PIDDosome is formed and either signals NF-kappaB activation and thus cell survival or alternatively triggers caspase-2 activation and apoptosis. PIDD (p53-induced protein with a death domain) is constitutively processed giving rise to a 48-kDa N-terminal fragment containing the leucine-rich repeats (LRRs, PIDD-N) and a 51-kDa C-terminal fragment containing the death domain (DD, PIDD-C). The latter undergoes further cleavage resulting in a 37-kDa fragment (PIDD-CC). Here we show that processing occurs at S446 (generating PIDD-C) and S588 (generating PIDD-CC) by an auto-processing mechanism similar to that found in the nuclear pore protein Nup98/96 and inteins. Auto-cleavage of PIDD determines the outcome of the downstream signaling events. Whereas initially formed PIDD-C mediates the activation of NF-kappaB via the recruitment of RIP1 and NEMO, subsequent formation of PIDD-CC causes caspase-2 activation and thus cell death. A non-cleavable PIDD mutant is unable to translocate from the cytoplasm to the nucleus and loses both activities. In this way, auto-proteolysis of PIDD might participate in the orchestration of the DNA damage-induced life and death signaling pathways.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159900-10087256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17159900-10500183,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17159900-9837928
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
197-208
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17159900-Amino Acid Sequence,
pubmed-meshheading:17159900-Apoptosis,
pubmed-meshheading:17159900-Carrier Proteins,
pubmed-meshheading:17159900-Caspase 2,
pubmed-meshheading:17159900-Cell Nucleus,
pubmed-meshheading:17159900-Cytoplasm,
pubmed-meshheading:17159900-DNA Damage,
pubmed-meshheading:17159900-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:17159900-Enzyme Activation,
pubmed-meshheading:17159900-HeLa Cells,
pubmed-meshheading:17159900-Humans,
pubmed-meshheading:17159900-Models, Biological,
pubmed-meshheading:17159900-Molecular Sequence Data,
pubmed-meshheading:17159900-Mutation,
pubmed-meshheading:17159900-NF-kappa B,
pubmed-meshheading:17159900-Signal Transduction
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pubmed:year |
2007
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pubmed:articleTitle |
Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-kappaB pathway.
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pubmed:affiliation |
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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