LAP2alpha-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit.

Lamina-associated polypeptide 2alpha (LAP2alpha) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2alpha 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 LAP2alpha 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 LAP2alpha protein levels were downregulated by proteasomal degradation. Although LAP2alpha 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 LAP2alpha and subsequent cell death. Our data show a role of LINT-25 and LAP2alpha during cell cycle exit, in which LINT-25 acts upstream of LAP2alpha.