SIRT6-PARP1 is involved in HMGB1 polyADP-ribosylation and acetylation and promotes chemotherapy-induced autophagy in leukemia.

In this study, we showed that knockdown of SIRT6 or PARP1 gene expression significantly inhibited HMGB1 cytoplasmic translocation and autophagy. Meanwhile, we found that SIRT6, an important upstream protein of PARP1, associated with PARP1, leading to the stimulation of polyADP-ribose polymerase activity. We further demonstrated that SIRT6 and PARP1 activation were required for chemotherapy-induced ADP-ribosylation of HMGB1 in leukemic cells and then influenced the acetylation of HMGB1, finally promoting the autophagy of leukemic cells mediated by HMGB1 translocation. These findings provide new insights into the mechanism of chemotherapeutic drug resistance. Targeting the HMGB1 translocation may overcome autophagy-related chemoresistance in leukemia. PMID: 31928132 [PubMed - as supplied by publisher]
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research