PML goes to the centrosome
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《细胞学杂志》
PML has at least 7 isoforms but most studies have used only one (PML4). Chang developed isoform-specific antibodies and saw that PML3 antibodies gave staining that coincided with that of centrosome proteins. Knock-down by siRNA of PML3, but not of other PML isoforms, resulted in centrosome amplification. And only PML3 interacted with and, when overexpressed, reduced the phosphorylation of Aurora A kinase.
It is known that in cells with activated Aurora A kinase there is a failure to inhibit Cdk2/cyclin E, leading to reduplication of centrosomes. Cells lacking PML had higher levels of Cdk2 kinase activity, which could explain the centrosome reduplication. What is signaling to PML from upstream is still mysterious, but the new findings certainly provide one possible explanation for why PML is lost in so many tumor types.
Reference:
Xu, Z.-X., et al. 2005. Mol. Cell. 17:721–732.(The promyelocytic leukemia gene (PML) ha)
It is known that in cells with activated Aurora A kinase there is a failure to inhibit Cdk2/cyclin E, leading to reduplication of centrosomes. Cells lacking PML had higher levels of Cdk2 kinase activity, which could explain the centrosome reduplication. What is signaling to PML from upstream is still mysterious, but the new findings certainly provide one possible explanation for why PML is lost in so many tumor types.
Reference:
Xu, Z.-X., et al. 2005. Mol. Cell. 17:721–732.(The promyelocytic leukemia gene (PML) ha)