title: CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by tristetraprolin.
abstract: Tristetraprolin (TTP) is an RNA-binding protein which can bind to the AU-rich elements (AREs) at the 3'-untranslated region (3'-UTR) of target mRNA and promote mRNA deadenylation and degradation. We have shown in a previous study that TTP regulates tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8), both of whose mRNAs have AREs in the 3'-UTR, in human pulmonary microvascular endothelial cells (HPMEC) through destabilizing target mRNAs, nevertheless, the mechanism by which TTP promotes mRNA decay remains unclear. Observations have indicated that TTP can interact with CAF1 (CNOT7/hCAF1 in human), a subunit of the CCR4-NOT complex with deadenylase activity. Another study illustrated that TTP can directly bind to CNOT1, the scaffold subunit of the CCR4-NOT complex. The present study showed that TTP bound to the AREs of ICAM-1 and IL-8 mRNAs and was coimmunoprecipitated with intracellular ICAM-1 and IL-8 mRNAs. TTP, CNOT7 and CNOT1 were coimmunoprecipitated in HPMEC. CNOT7 silencing stabilized ICAM-1 and IL-8 mRNAs and increased ICAM-1 and IL-8 production following TNF-α stimulation. These results, together with our previous study, suggest that CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by TTP in HPMEC.
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, 182 Northern Tongguan Road, Lianyungang 222002, China. Electronic address: shijiaxin919@126.com.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, 182 Northern Tongguan Road, Lianyungang 222002, China. Electronic address: ljssm1118@sina.com.
authors.forename: Jia-Shu
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, 182 Northern Tongguan Road, Lianyungang 222002, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, 182 Northern Tongguan Road, Lianyungang 222002, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, 182 Northern Tongguan Road, Lianyungang 222002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005095:Exoribonucleases; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051816:Tristetraprolin / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C489780:CNOT8 protein, human; C508606:CXCL8 protein, human; C573420:ICAM1 protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D012097:Repressor Proteins; C439524:TNF protein, human; D014157:Transcription Factors; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; C497552:ZFP36 protein, human; D018799:Intercellular Adhesion Molecule-1; C545829:CNOT7 protein, human; D005095:Exoribonucleases
keywords: AU-rich element (ARE); CNOT1; CNOT7/hCAF1; ICAM-1; IL-8; Tristetraprolin (TTP)