Figure 2.

Intranuclear proteasome movements in mammalian cells in response to stress. The double line represents the nuclear envelope with nuclear pores. A, LLPS-driven nuclear proteasome foci are formed upon hyperosmotic and nucleolar stress resulting in the accumulation of nonincorporated ribosomal proteins (76). SIPAN in the nucleus and JUNQ at the ER/nuclear envelope are formed upon amino acid starvation and proteasome inhibition, respectively (75, 78). Rad23B with two ubiquitin-associated domains binds polyubiquitin chains of proteasomal substrates and mediates multivalent interactions for LLPS. ATPase p97/VCP/Cdc48 assists in foci clearance upon stress relief by removing polyubiquitinated proteins (76). B, intranuclear p62 foci are induced by inhibition of Crm1/Xpo1–mediated nuclear export, heat, and oxidative stress. Proteasomes are recruited to the periphery of p62 foci (77). ER, endoplasmic reticulum; LLPS, liquid–liquid phase separation.