Stimulation of polo-like kinase 3 mRNA decay by tristetraprolin.
Polo-like protein kinase 3 (Plk3) has been proposed to regulate entry into S phase and promote apoptosis in response to oxidative stress. Its mRNA contains three AU-rich elements (AREs) in its 3' untranslated region (3'-UTR) that can contribute to the rapid degradation of labile transcripts. We investigated the possibility that tristetraprolin (TTP), a tandem CCCH zinc finger protein, could promote the decay of Plk3 transcripts. TTP is known to stimulate the deadenylation and decay of mRNAs possessing one or more copies of the consensus nonamer motif UUAUUUAUU. In stable mouse fibroblast cell lines derived from wild-type and TTP knockout littermates, the decay of Plk3 transcripts after serum stimulation was slowed in the absence of TTP. The specificity of TTP for promoting the degradation of Plk3 was demonstrated by the unaltered decay of Plk3 mRNA in cell lines deficient in the TTP family members ZFP36L1 and ZFP36L2. We also found that the AREs present in the Plk3 transcript were essential for both the binding of TTP to the 3'-UTR and promoting the destruction of target transcripts in cotransfection experiments. The regulation of Plk3 mRNA stability by TTP may influence the control of the cell cycle by this protein kinase.
Horner
Thierry J
TJ
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Lai
Wi S
WS
Stumpo
Deborah J
DJ
Blackshear
Perry J
PJ
D020413:3' Untranslated Regions; D000818:Animals; D051817:Butyrate Response Factor 1; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D051816:Tristetraprolin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; D051817:Butyrate Response Factor 1; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051816:Tristetraprolin; C497553:Zfp36 protein, mouse; C488431:Zfp36l1 protein, mouse; C093328:Plk3 protein, mouse; D017346:Protein Serine-Threonine Kinases