Global regulation of the conjugating machinery. A) The Gam1 protein from CELO adenovirus reduces E1 and E2 enzyme levels . The resulting global desumoylation correlates with increased transcriptional activity, which is due, at least in part, to desumoylation of transcription factors such as Sp3. B) H2O2 inhibits SUMO conjugation by inducing the formation of a disulfide bond between the catalytic cysteines of the E1 and E2 enzymes. Depending on the source and dose of H2O2 (applied exogenously or produced endogenously) this results in local desumoylation of specific proteins or global desumoylation .