Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival

The immediate early protein tristetraprolin (TTP) is required to prevent in appropriate 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 desta bilize the TNF-alpha mRNA, TTP and the closely related TIS11b and TIS11d pr oteins are evolutionarily conserved, however, and induced transiently in va rious cell types by numerous diverse stimuli, suggesting that they have add itional functions. Supporting this idea, continuous expression of each TTP/ TIS11 protein at physiological levels causes apoptotic cell death. By vario us criteria, this cell death appears analogous to apoptosis induced by cert ain oncoproteins. It is also dependent upon the zinc fingers, suggesting th at it involves action on appropriate cellular targets. TTP but not TIS11b o r TIS11d also sensitizes cells to induction of apoptosis by TNF-alpha. The data suggest that the TTP and TIS11 immediate early proteins have similar b ut distinct effects on growth or survival pathways, and that TTP might infl uence TNF-alpha regulation at multiple levels.