The role of charged multivesicular body protein 5 in programmed cell death in leukemic cells.

The Homo sapiens charged multivesicular body protein 5 (CHMP5) is a member of the multivesicular body, which serves as an anti-apoptotic protein and is thought to participate in leukemogenesis. In this study, a short-hairpin RNA-based RNA interference approach was used to inhibit the expression of CHMP5 in the leukemic cell line U937. After CHMP5 was inhibited, antibody microarray and western blot analysis were used to study the changes in the programmed cell death (PCD) pathway. PCD can be classified into three types: apoptosis, necrosis, and autophagy. Results showed that caspase 3 was activated in CHMP5-deficient U937 cells, indicating that the apoptotic pathway was activated, although neither the intrinsic nor the extrinsic apoptotic pathways were activated. Our results also showed that the Granzyme B/Perforin apoptotic pathway was activated by CHMP5 silencing. Necrosis is activated by caspase-independent executioners. In this study, we showed that the apoptosis-inducing protein-mediated necrotic PCD pathway is activated after CHMP5 inhibition. It was found that autophagic PCD did not occur in CHMP5-deficient U937 cells. In conclusion, after CHMP5 inhibition, both Granzyme B/Perforin apoptotic pathway and apoptosis-inducing factor-mediated necrotic pathway were activated, while autophagic pathway was not activated.

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