CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by tristetraprolin

Cell Signal. 2014 Nov;26(11):2390-6. doi: 10.1016/j.cellsig.2014.07.020. Epub 2014 Jul 16.


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.

Keywords: AU-rich element (ARE); CNOT1; CNOT7/hCAF1; ICAM-1; IL-8; Tristetraprolin (TTP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • RNA Stability / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tristetraprolin / biosynthesis*
  • Tristetraprolin / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • CNOT8 protein, human
  • CXCL8 protein, human
  • ICAM1 protein, human
  • Interleukin-8
  • RNA, Messenger
  • TNF protein, human
  • Transcription Factors
  • Tristetraprolin
  • Tumor Necrosis Factor-alpha
  • ZFP36 protein, human
  • Intercellular Adhesion Molecule-1
  • CNOT7 protein, human