Abstract

CANAS DAVILA, Carlos Alberto  and  IGLESIAS GAMARRA, Antonio. Tristhetraproline: TNF-a regulating protein, of pathogenic importance in rheumatoid arthritis. Acta Med Colomb [online]. 2006, vol.31, n.3, pp.113-119. ISSN 0120-2448.

he tristetraprolin (TTP) family of CCCH tandem zinc-finger proteins is composed of three known members in mammalians, with a fourth member recently identified in frogs and fish. Although TTP was first cloned more than 15 years ago as a transcriptional factor, it is only in the past few years that the physiological function for the protein has been discovered. TTP is now known to bind to the so-called class II AU-rich elements within the mRNAs that encode Tumour Necrosis Factor-a (TNF-a) and granulocyte/macrophage colony-stimulating factor (GM-CSF). In both cases, this binding results in destabilization of the mRNA and decreased secretion of the protein. Recent evidence suggests that TTP can accomplish this accelerated mRNA degradation by first promoting removal of the polyadenylated tail from the mRNA (deadenylation). TTP deficient mice develop a deep inflammatory syndrome with erosive arthritis, autoimmunity and myeloid hyperplasia. In patients with rheumatoid arthritis a low TTP/TNF-a gene expression ratio could indicate failure to produce adequate amounts of TTP in response to increased TNF-a production. Inappropriate TTP production may be one factor that contributes to higher disease activity. Understanding the posttranscriptional regulation of TNF-a biosynthesis is important for the development of new treatment strategies in rheumatoid arthritis and other diseases which TNF-a has pathogenic importance.

Keywords : tristetraprolin; tumour necrosis factor-a; rheumatoid arthritis.

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