The promyelocytic leukemia (PML) protein suppresses cyclin D1 protein production by altering the nuclear cytoplasmic distribution of cyclin D1 mRNA

被引:82
作者
Lai, HK [1 ]
Borden, KLB [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA
关键词
PML; nuclear bodies; APL; RING; RNA transport;
D O I
10.1038/sj.onc.1203473
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The majority of the promyelocytic leukemia (PML) protein is present in nuclear bodies which are altered in several pathogenic conditions including acute promyelocytic leukemia. PML nuclear bodies are found in nearly all cells yet their function remains unknown. Here, we demonstrate that PML and the eukaryotic initiation factor 4E (eIF-4E) co-localize and co-immunopurify. eIF-4E is involved in nucleocytoplasmic transport of specific mRNAs including cyclin D1, eIF-4E overexpression leads to increased cyclin D1 protein levels;,whereas, overexpression of PML leads to decreased cyclin D1 le,els. Neither PML nor eIF-4E cause significant changes in cyclin D1 mRNA levels. The association with eIF-4E led us to investigate if PML could alter mRNA distribution as a possible post-transcriptional mechanism for suppressing cyclin D1 production. We show that overexpression of PML results in nuclear retention of cyclin D1 mRNA and that intact PR-IL nuclear bodies are required. Addition of eIF-4E overcomes PML induced retention and alters the morphology of PML bodies suggesting a mechanism by which eIF-4E can modulate PML function. These results raise the possibility that PML nuclear bodies may participate in the regulation of nucleocytoplasmic transport of specific mRNAs.
引用
收藏
页码:1623 / 1634
页数:12
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