Ikaros is degraded by proteasome-dependent mechanism in the early phase of apoptosis induction

Ikaros is an important transcription factor involved in the development and differentiation of hematopoietic cells. In this work, we found that chemotherapeutic drugs or ultraviolet radiation (UV) treatment could reduce the expression of full-length Ikaros (IK1) protein in less than 3 h in leukemic NB4, Kasumi-1 and Jurkat cells, prior to the activation of caspase-3. Etoposide treatment could not alter the mRNA level of IK1 but it could shorten the half-life of IK1. Co-treatment with the proteasome inhibitor MG132 or epoxomicin but not calpain inhibitor calpeptin inhibited etoposide-induced Ikaros downregulation. Overexpression of IK1 could accelerate etoposide-induced apoptosis in NB4 cells, as evidenced by the increase of Annexin V positive cells and the more early activation of caspase 3. To our knowledge, this is the first report to show that upon chemotherapy drugs or UV treatment, IK1 could be degraded via the proteasome system in the early phase of apoptosis induction. These data might shed new insight on the role of IK1 in apoptosis and the post-translational regulation of IK1.

Research highlights
► Chemotherapeutic drugs or UV treatment reduces Ikaros prior to caspase-3 activation.
► Etoposide treatment does not alter the mRNA but shortens the half-life of Ikaros.
► MG132 or epoxomicin but not calpeptin inhibits etoposide-induced Ikaros degradation.
► Overexpression of Ikaros accelerates etoposide-induced apoptosis in NB4 cells.