LAP2-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit

Lamina-associated polypeptide 2 (LAP2) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2 interacts with A-type lamins and retinoblastoma protein and regulates cell cycle progression via the E2F-Rb pathway. Using yeast two-hybrid analysis and three independent in vitro binding assays we identified a new LAP2 interaction partner of hitherto unknown functions, which we termed LINT-25. LINT-25 protein levels were upregulated during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation. Upon cell cycle exit LINT-25 accumulated in heterochromatin foci, and LAP2 protein levels were downregulated by proteasomal degradation. Although LAP2 was not required for the upregulation and reorganization of LINT-25 during cell cycle exit, transient expression of LINT-25 in proliferating cells caused loss of LAP2 and subsequent cell death. Our data show a role of LINT-25 and LAP2 during cell cycle exit, in which LINT-25 acts upstream of LAP2.