Depletion of the AP-1 repressor JDP2 induces cell death similar to apoptosis.
JDP2 is a ubiquitously expressed nuclear protein that efficiently represses the activity of the transcription factor AP-1. Thus far, all studies of JDP2 function have relied on the ectopic expression of the protein. In this study, we use a different approach: depletion of JDP2 from cells. Specific depletion of JDP2 resulted in p53-independent cell death that resembles apoptosis and was evident at 72 h. The death mechanism was caspase dependent as the cells could be rescued by treatment with caspase inhibitor zVAD. Our studies suggest that JDP2 functions as a general survival protein, not only following UV-irradiation, as reported earlier, but also under normal culture conditions. Thus, our data support that JDP2 is a cellular survival protein whose presence is necessary for normal cellular function.
Lerdrup
M
M
Apoptosis Department, Institute of Biological Cancer Research, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Holmberg
C
C
Dietrich
N
N
Shaulian
E
E
Herdegen
T
T
Jäättelä
M
M
Kallunki
T
T
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D016133:Polymerase Chain Reaction; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D017931:DNA Primers; D018076:DNA, Complementary; C491387:JDP2 protein, human; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007770:L-Lactate Dehydrogenase