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Interaction of AU-rich sequence binding proteins with actin: Possible involvement of the actin cytoskeleton in lymphokine mRNA turnover

✍ Scribed by Tamás Henics; Eszter Nagy; Júlia Szekeres-Barthó


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
277 KB
Volume
173
Category
Article
ISSN
0021-9541

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✦ Synopsis


In the current study, we report that cytochalasin-induced disruption of microfilaments stabilizes lymphokine mRNAs in activated human peripheral blood lymphocytes. Parallel with this, a dose-and time-dependent increase in AU-rich sequence binding protein (AUPB) activities is apparent in the nonionic detergentresistant fractions of these cells, suggesting that cytochalasin-induced modulation of lymphokine mRNA stability might be mediated through cytoplasmic AUBPs. We provide evidence that some of the AUBPs can be immunoprecipitated with anti-actin antibodies, implicating the potential of these proteins to associate with the actin-based cytoskeleton in vivo. Moreover, disruption of the microfilament network by cytochalasins produces increased immunoprecipitable actin-AUBP complexes in the detergent-resistant cytoplasmic subfractions of lymphocytes. We show that cytochalasin-induced changes in AUBP activities are parallel with their higher binding affinity to RNA containing AU-rich instability sequence element as judged by in vitro competition and in vivo ultraviolet-crosslinking analysis. Correlation of these findings with changes in mRNA stability indicates that the actin cytoskeleton may play a physiologically important role in posttranscriptional regulation of lymphokine gene expression during early lymphocyte activation.