3.2. PA28γ in nuclear dynamics

While varying levels of chromatin compaction result in euchromatin and heterochromatin, nuclear bodies structure interchromatin as well [68]. PA28γ and 20S proteasomes have been found to be physically associated with nuclear structures such as nuclear speckles [40], Cajal bodies (CBs) [41], and PML bodies [69, 70] or have been associated with nuclear survival functions and chromosomal stability [71].

Nuclear speckles as subnuclear interchromatin domains are enriched in components of the pre-mRNA splicing machinery. 20S proteasomes and PA28γ co-localize in such NS structures [40]. PSME3 silencing affects NS organization and recruitment of splicing factors of the SR family to transcription sites. Proteasome inhibitors promote the accumulation of SC35 in NS. Contributions of UIPP and/or UPS to NS protein dynamics seem to be crucial for nuclear speckle function.

CBs are sites of assembly of small nuclear ribonucleoproteins and small noncoding RNA traffic [72]. They are specific nuclear targets of the cellular stress response [41]. It has been shown that UV-C irradiation induces a stable association of PA28γ with coilin, the intrinsically disordered marker protein of CBs. The accumulation of PA28γ correlates with the disruption of CBs. Apart from its canonical targeting via Mdm2, the unstructured nature of coilin and its association with PA28γ might be the first evidence for coilin targeting via UIPP.
