title: RNA-binding Protein PCBP2 Regulates p73 Expression and p73-dependent Antioxidant Defense.
abstract: TAp73, a member of the p53 family tumor suppressors, plays a critical rule in tumor suppression and neuronal development. However, how p73 activity is controlled at the posttranscriptional level is not well understood. Here, we showed that TAp73 activity is regulated by RNA-binding protein PCBP2. Specifically, we found that knockdown or knock-out of PCBP2 reduces, whereas ectopic expression of PCBP2 increases, TAp73 expression. We also showed that PCBP2 is necessary for p73 mRNA stability via the CU-rich elements in p73 3'-UTR. To uncover the biological relevance of PCBP2-regulated TAp73 expression, we showed that ectopic expression of PCBP2 inhibits, whereas knockdown or knock-out of PCBP2 increases, the production of reactive oxygen species (ROS) in a TAp73-dependent manner. Additionally, we found that glutaminase 2 (GLS2), a modulator of p73-dependent antioxidant defense, is also involved in PCBP2-regulated ROS production. Moreover, we generated PCBP2-deficient mice and primary mouse embryonic fibroblasts (MEFs) and showed that loss of PCBP2 leads to decreased p73 expression and, subsequently, increased ROS production and accelerated cellular senescence. Together, our data suggest that PCBP2 regulates p73 expression via mRNA stability and p73-dependent biological function in ROS production and cellular senescence.
authors.affiliation: From the Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 95616.
authors.forename: Cong
authors.initials: C
authors.lastname: Ren
authors.affiliation: From the Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 95616 jinzhang@ucdavis.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 95616.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yan
authors.affiliation: From the Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 95616.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 95616 xbchen@ucdavis.edu.
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000637:Transaminases / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000975:Antioxidants; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501904:Pcbp2 protein, mouse; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000637:Transaminases; C020656:glutamine-pyruvate aminotransferase
keywords: PCBP2; cellular senescence; mRNA decay; p53; p73; reactive oxygen species (ROS)