期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1994
卷号：91
期号：3
页码：1178-1182
DOI：10.1073/pnas.91.3.1178
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recently, we described a recurrent variant translocation, t(11;17)(q23;q21), in acute promyelocytic leukemia (APL) which juxtaposes PLZF, a gene encoding a zinc finger protein, to RARA, encoding retinoic acid receptor alpha (RAR alpha). We have now cloned cDNAs encoding PLZF-RAR alpha chimeric proteins and studied their transactivating activities. In transient-expression assays, both the PLZF(A)-RAR alpha and PLZF(B)-RAR alpha fusion proteins like the PML-RAR alpha protein resulting from the well-known t(15;17) translocation in APL, antagonized endogenous and transfected wild-type RAR alpha in the presence of retinoic acid. Cotransfection assays showed that a significant repression of RAR alpha transactivation activity was obtained even with a very low PLZF-RAR alpha-expressing plasmid concentration. A "dominant negative" effect was observed when PLZF-RAR alpha fusion proteins were cotransfected with vectors expressing RAR alpha and retinoid X receptor alpha (RXR alpha). These abnormal transactivation properties observed in retinoic acid-sensitive myeloid cells strongly implicate the PLZF-RAR alpha fusion proteins in the molecular pathogenesis of APL.
