title: Positive and negative feedback loops in the p53 and mRNA 3' processing pathways.
abstract: Although the p53 network has been intensively studied, genetic analyses long hinted at the existence of components that remained elusive. Recent studies have shown regulation of p53 at the mRNA level mediated via both the 5' and the 3' untranslated regions and affecting the stability and translation efficiency of the p53 mRNA. Here, we provide evidence of a feedback loop between p53 and the poly(A)-specific ribonuclease (PARN), in which PARN deadenylase keeps p53 levels low in nonstress conditions by destabilizing p53 mRNA, and the UV-induced increase in p53 activates PARN deadenylase, regulating gene expression during DNA damage response in a transactivation-independent manner. This model is innovative because it provides insights into p53 function and the mechanisms behind the regulation of mRNA 3' end processing in different cellular conditions.
authors: Chemistry Department, Hunter College and Graduate Center, City University of New York, New York, NY 10065, USA.
authors: Emral
authors: E
authors: Devany
authors: Xiaokan
authors: X
authors: Zhang
authors: Ji Yeon
authors: JY
authors: Park
authors: Bin
authors: B
authors: Tian
authors: Frida Esther
authors: FE
authors: Kleiman
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063307:AU Rich Elements / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D005095:Exoribonucleases / Q000378:metabolism; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D011485:Protein Binding / Q000235:genetics; D026721:RNA 3' End Processing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D005095:Exoribonucleases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53
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