Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival.
The immediate early protein tristetraprolin (TTP) is required to prevent inappropriate production of the cytokine TNF-alpha, and is a member of a zinc finger protein family that is associated with RNA binding. TTP expression is induced by TNF-alpha, and evidence indicates that TTP can bind and destabilize the TNF-alpha mRNA. TTP and the closely related TIS11b and TIS11d proteins are evolutionarily conserved, however, and induced transiently in various cell types by numerous diverse stimuli, suggesting that they have additional functions. Supporting this idea, continuous expression of each TTP/TIS11 protein at physiological levels causes apoptotic cell death. By various criteria, this cell death appears analogous to apoptosis induced by certain oncoproteins. It is also dependent upon the zinc fingers, suggesting that it involves action on appropriate cellular targets. TTP but not TIS11b or TIS11d also sensitizes cells to induction of apoptosis by TNF-alpha. The data suggest that the TTP and TIS11 immediate early proteins have similar but distinct effects on growth or survival pathways, and that TTP might influence TNF-alpha regulation at multiple levels.
Johnson
B A
BA
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Geha
M
M
Blackwell
T K
TK
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005246:Feedback; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009857:Oncogenes; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; C497552:ZFP36 protein, human; C497553:Zfp36 protein, mouse