Roles of GINS2 in K562 human chronic myelogenous leukemia and NB4 acute promyelocytic leukemia cells.

GINS2 has been found to be closely related to cell proliferation, survival and maintenance of genomic integrity in addition to the induction of polyploidy. However, the molecular mechanisms of GINS2-mediated tumor regression have not been fully elucidated. Our study showed that GINS2 interacted with PML-C (a structural domain of PML, which is a cutting product of PML-RARα) as demonstrated by yeast two-hybrid assay and co-immunoprecipitation, and PML (NLS-) also interacted with GINS2 by co-immunoprecipitation. Following transfection with plasmids expressing GINS2 siRNA, the apoptosis and cell cycle distribution were determined by flow cytometry. The results revealed that K562 chronic myelocytic leukemia cells and NB4 acute promyelocytic leukemia cells were arrested in the G2 phase. Western blot assay indicated that the expression of cyclin A, cyclin D1 and cyclin B1 was decreased, and cyclin B1 was localized in the cytoplasm after GINS2 knockdown as demonstrated by immunofluorescence staining. The expression of the apoptosis-related protein Bcl-2 was decreased but that of Bax was increased in the cells transfected with GINS2 siRNA. The percentage of apoptotic cells was increased as detected by flow cytometry. Our findings demonstrated that GINS2 plays an important role in apoptosis and may function via the p38MAPK signaling pathway.