PodcastPosttranslational Modifications

Science Signaling Podcast: 9 June 2015

See allHide authors and affiliations

Sci. Signal.  09 Jun 2015:
Vol. 8, Issue 380, pp. pc14
DOI: 10.1126/scisignal.aac6344

You are currently viewing the abstract.

View Full Text


This Podcast features an interview with Guy Salvesen, senior author of a Research Article that appears in the 9 June 2015 issue of Science Signaling, about how the drug arsenic trioxide causes degradation of the oncogenic protein associated with promyelocytic leukemia. Promyelocytic leukemia is characterized by a chromosomal translocation that causes promyelocytes to produce a fusion protein consisting of the promyelocytic leukemia protein (PML) fused to the retinoic acid receptor RARα. Whereas PML is a tumor suppressor, PML-RARα promotes oncogenesis. Arsenic trioxide is used to treat promyelocytic leukemia because it induces aggregation and degradation of PML and PML-RARα. Arsenic trioxide–induced degradation of PML involves both sumoylation and ubiquitylation of PML. Fasci et al. found that SUMO2 was continuously conjugated to and removed from Lys65 of PML in untreated cells. Treatment with arsenic trioxide caused SUMO1 to be conjugated to Lys65 instead, which resulted in the attachment of SUMO2 chains on Lys160 and subsequent ubiquitylation of PML and reorganization of PML-containing nuclear bodies.

View Full Text