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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2007-3-19
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pubmed:abstractText |
Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA)-15 is an anti-apoptotic protein whose expression is increased in several cancer cells and following experimental skin carcinogenesis. Exposure of untransfected C5N keratinocytes and transfected HEK293 cells to phorbol esters (12-O-tetradecanoylphorbol-13-acetate (TPA)) increased PED/PEA-15 cellular content and enhanced its phosphorylation at serine 116 in a time-dependent fashion. Ser-116 --> Gly (PED(S116G)) but not Ser-104 --> Gly (PED(S104G)) substitution almost completely abolished TPA regulation of PED/PEA-15 expression. TPA effect was also prevented by antisense inhibition of protein kinase C (PKC)-zeta and by the expression of a dominant-negative PKC-zeta mutant cDNA in HEK293 cells. Similar to long term TPA treatment, overexpression of wild-type PKC-zeta increased cellular content and phosphorylation of WT-PED/PEA-15 and PED(S104G) but not of PED(S116G). These events were accompanied by the activation of Ca2+-calmodulin kinase (CaMK) II and prevented by the CaMK blocker, KN-93. At variance, the proteasome inhibitor lactacystin mimicked TPA action on PED/PEA-15 intracellular accumulation and reverted the effects of PKC-zeta and CaMK inhibition. Moreover, we show that PED/PEA-15 bound ubiquitin in intact cells. PED/PEA-15 ubiquitinylation was reduced by TPA and PKC-zeta overexpression and increased by KN-93 and PKC-zeta block. Furthermore, in HEK293 cells expressing PED(S116G), TPA failed to prevent ubiquitin-dependent degradation of the protein. Accordingly, in the same cells, TPA-mediated protection from apoptosis was blunted. Taken together, our results indicate that TPA increases PED/PEA-15 expression at the post-translational level by inducing phosphorylation at serine 116 and preventing ubiquitinylation and proteosomal degradation.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Benzylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/KN 93,
http://linkedlifedata.com/resource/pubmed/chemical/PEA15 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AlberobelloA TeresaAT,
pubmed-author:BarbagalloAlessia P MAP,
pubmed-author:BeguinotFrancescoF,
pubmed-author:EspositoIolandaI,
pubmed-author:FioryFrancescaF,
pubmed-author:FormisanoPietroP,
pubmed-author:IovinoSalvatoreS,
pubmed-author:MieleClaudiaC,
pubmed-author:OrienteFrancescoF,
pubmed-author:PerfettiAnnaA,
pubmed-author:TeperinoRaffaeleR,
pubmed-author:UngaroPaolaP
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8648-57
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pubmed:dateRevised |
2009-4-7
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pubmed:meshHeading |
pubmed-meshheading:17227770-Benzylamines,
pubmed-meshheading:17227770-Calcium,
pubmed-meshheading:17227770-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:17227770-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:17227770-Gene Expression Regulation,
pubmed-meshheading:17227770-Humans,
pubmed-meshheading:17227770-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17227770-Phorbol Esters,
pubmed-meshheading:17227770-Phosphoproteins,
pubmed-meshheading:17227770-Phosphorylation,
pubmed-meshheading:17227770-Proteasome Endopeptidase Complex,
pubmed-meshheading:17227770-Protein Binding,
pubmed-meshheading:17227770-Protein Kinase C,
pubmed-meshheading:17227770-Protein Kinase Inhibitors,
pubmed-meshheading:17227770-Protein Processing, Post-Translational,
pubmed-meshheading:17227770-Sulfonamides,
pubmed-meshheading:17227770-Tetradecanoylphorbol Acetate,
pubmed-meshheading:17227770-Ubiquitin
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pubmed:year |
2007
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pubmed:articleTitle |
Phorbol esters induce intracellular accumulation of the anti-apoptotic protein PED/PEA-15 by preventing ubiquitinylation and proteasomal degradation.
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pubmed:affiliation |
Dipartimento di Biologia e Patologia cellulare e Molecolare (DBPCM), Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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