Characterization of endogenous human promyelocytic leukemia isoforms
Characterization of endogenous human promyelocytic leukemia isoforms
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DOI：
10.1158/0008-5472.can-05-3792
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发表时间：
2006-06-15
期刊：
影响因子：
11.2
通讯作者：
de The, Hugues
中科院分区：
文献类型：
--
作者：
Condemine, Wilfried;Takahashi, Yuki;de The, Hugues
早幼粒细胞白血病（PML）涉及多种功能，包括控制TP 53功能和调节细胞衰老。Sumolated PML是成熟PML小体的组织者，将各种蛋白质募集到这些核结构域上。预测PML基因编码多种蛋白质同种型。其中只有一个，PML-IV，过度表达，促进人类二倍体成纤维细胞的衰老，而PML-III提出了专门与中心体相互作用。我们表明，所有的PML亚型蛋白表达的细胞系或原代细胞。出乎意料的是，我们发现PML-III、PML-IV和PML-V与PML-I/II相比在数量上是次要的同种型，并且不能证实PML-III的中心体靶向。每种亚型的稳定表达，在pml空背景下，产生不同的亚细胞定位模式，表明与其他RBCC/TRIM蛋白一样，PML的COOH末端结构域参与与特定细胞组分的相互作用。只有PML-I和PML-V的同种型特异性序列在人和小鼠之间高度保守。PML-I包含所有保守的外显子，并且比PML-IV表达更丰富，这表明它是PML功能的关键贡献者。
Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s).