Condemine Wilfried, Takahashi Yuki, Le Bras Morgane, de Thé Hugues
CNRS/Université de Paris 7 UMR7151, Equipe labellisée par la Ligue Contre le Cancer, Hôpital St. Louis, 1 Av. C. Vellefaux 75475, Paris Cedex 10, France.
J Cell Sci. 2007 Sep 15;120(Pt 18):3219-27. doi: 10.1242/jcs.007492.
The promyelocytic leukemia (PML) tumour suppressor is the organiser of PML nuclear bodies, which are domains the precise functions of which are still disputed. We show that upon several types of stress, endogenous PML proteins form nucleolar caps and eventually engulf nucleolar components. Only two specific PML splice variants (PML-I and PML-IV) are efficiently targeted to the nucleolus and the abundant PML-I isoform is required for the targeting of endogenous PML proteins to this organelle. We identified a nucleolar targeting domain within the evolutionarily conserved C-terminus of PML-I. This domain contains a predicted exonuclease III fold essential for the targeting of the PML-I C-terminus to nucleolar fibrillar centres. Furthermore, spontaneous or oncogene retrieval-induced senescence is associated with the formation of very large PML nuclear bodies that initially contain nucleolar components. Later, poly-ubiquitin conjugates are found on the outer shell or within most of these senescence-associated PML bodies. Thus, unexpectedly, the scarcely studied PML-I isoform links PML bodies, nucleolus, senescence and proteolysis.
早幼粒细胞白血病（PML）肿瘤抑制因子是PML核体的组织者，PML核体是一些结构域，其确切功能仍存在争议。我们发现，在几种类型的应激情况下，内源性PML蛋白会形成核仁帽，并最终吞噬核仁成分。只有两种特定的PML剪接变体（PML-I和PML-IV）能有效地靶向核仁，并且内源性PML蛋白靶向该细胞器需要丰富的PML-I异构体。我们在PML-I进化保守的C末端鉴定出一个核仁靶向结构域。该结构域包含一个预测的核酸外切酶III折叠结构，这对于PML-I C末端靶向核仁纤维中心至关重要。此外，自发或癌基因诱导的衰老与最初包含核仁成分的非常大的PML核体的形成有关。后来，在这些衰老相关PML体的外壳或大部分内部发现了多聚泛素缀合物。因此，出乎意料的是，很少被研究的PML-I异构体将PML体、核仁、衰老和蛋白水解联系在一起。
