Technical CommentsPosttranslational Modifications

Response to Comment on “SUMO deconjugation is required for arsenic-triggered ubiquitylation of PML”

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Science Signaling  09 Aug 2016:
Vol. 9, Issue 440, pp. tc2
DOI: 10.1126/scisignal.aad9777


Arsenic trioxide chemotherapy cures acute promyelocytic leukemia by inducing the ubiquitylation of an oncogenic fusion protein containing promyelocytic leukemia protein (PML) subsequent to modification of PML by SUMO1 and SUMO2. We proposed that the SUMO switch at Lys65 of PML enhanced subsequent SUMO2 conjugation to Lys160 and consequent RNF4-dependent ubiquitylation of PML. Ferhi et al. note differences between their experimental system and ours regarding the outcome and mechanisms of SUMO-dependent PML signaling. When confronted by apparently contradictory data, it is appropriate to drill down to where the differences could lie.

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