{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:24:41Z","timestamp":1790630681499,"version":"4.1.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>P-glycoprotein is a 170-kd glycosylated transmembrane protein, expressed in a variety of human cells and belonging to the adenosine triphosphate\u2013binding cassette transporter family, whose membrane expression is functionally associated with the multidrug resistance phenotype. However, the mechanisms underlying the regulation of P-glycoprotein functions remain unclear. On the basis of some evidence suggesting P-glycoprotein\u2013actin cytoskeleton interaction, this study investigated the association of P-glycoprotein with ezrin, radixin, and moesin, a class of proteins that cross-link actin filaments with plasma membrane in a human cell line of lymphoid origin and that have been shown to link other ion-pump\u2013related proteins. To this purpose, a multidrug-resistant variant of CCRF-CEM cells (CEM-VBL100) was used as a model to investigate the following: (1) the cellular localizations of P-glycoprotein and ezrin, radixin, and moesin and their molecular associations; and (2) the effects of ezrin, radixin, and moesin antisense oligonucleotides on multidrug resistance and P-glycoprotein function. The results showed that: (1) P-glycoprotein colocalized and coimmunoprecipitated with ezrin, radixin, and moesin; and (2) treatment with antisense oligonucleotides for ezrin, radixin, and moesin restored drug susceptibility consistently with inhibition of both drug efflux and actin\u2013P-glycoprotein association and induction of cellular redistribution of P-glycoprotein. These data suggest that P-glycoprotein association with the actin cytoskeleton through ezrin, radixin, and moesin is key in conferring to human lymphoid cells a multidrug resistance phenotype. Strategies aimed at inhibiting P-glycoprotein\u2013actin association may be helpful in increasing the efficiency of both antitumor and antiviral therapies.<\/jats:p>","DOI":"10.1182\/blood.v99.2.641","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"641-648","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":119,"title":["P-glycoprotein\u2013actin association through ERM family proteins: a role in P-glycoprotein function in human cells of lymphoid origin"],"prefix":"10.1182","volume":"99","author":[{"given":"Francesca","family":"Luciani","sequence":"first","affiliation":[{"name":"From the Laboratory of Immunology and Ultrastructures, Istituto Superiore di Sanita\u0300, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Molinari","sequence":"additional","affiliation":[{"name":"From the Laboratory of 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