Caspases Mediate Retinoic Acid–Induced Degradation of the Acute Promyelocytic Leukemia PML/RARα Fusion Protein

摘要: All- trans -retinoic acid (RA) treatment induces morphological remission in acute promyelocytic leukemia (APL) patients carrying the t(15;17) and expressing PML/RARα product by inducing terminal differentiation of leukemic clone. RA downregulation reorganization PML-nuclear bodies. These events have been proposed to be essential for induction APL cell RA. Here, we show that APL-derived NB4 line as well myeloid precursor U937 cells (U937/PR9) blasts from patients, fusion protein is cleaved a caspase 3–like activity induced treatment. In fact, detectable after treatment, selective inhibitor peptides are able prevent RA-induced degradation vivo vitro. Using recombinant caspases deletion mutants mapped 3 cleavage site (Asp 522) within α-helix region PML component protein. The extent directly correlates with ability restore normal nuclear bodies (NBs) pattern. However, not prevented persistence occurs absence normally structured NBs. results indicate involved conferring sensitivity reassembly NBs consequence disappearance PML/RARα.