Abstract
PA28γ, a nuclear regulator of the 20S proteasome, is involved in the control of several essential cellular processes, such as cell proliferation and nuclear organization, including Cajal body dynamics. However, the mechanisms controlling PA28γ function in the regulation of nuclear architecture are not known. Here we identify through a SILAC-based proteomics approach a specific and prominent interaction partner of PA28γ, called FAM192A/PIP30. We show that the PA28γ/PIP30 complex is stabilized by Casein Kinase 2-dependent phosphorylation of the PIP30 C-terminal region. PIP30 depletion reduces the number of Cajal bodies in human cells similar to PA28γ overexpression. Importantly, PIP30 depletion also results in the accumulation of PA28γ in residual Cajal body structures, which correlates with an increased interaction between PA28γ and coilin. Altogether our data identify the first regulator of PA28γ, which plays a critical role in Cajal body dynamics by antagonizing the formation of PA28γ/coilin complexes.