The promyelocytic leukemia gene (PML) has “too many things it is involved in,” says Kun-Sang Chang (University of Texas MD Anderson Cancer Center, Houston, TX). But now Chang, Zhi-Xiang Xu, and colleagues have added another function: the PML3 isoform prevents centrosome reduplication.
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...
