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Small ubiquitin-like modifier (SUMO) 2/3 is known to conjugate to substrates in response to a variety of cellular stresses. However, whether and bow SUMO2/3-specific proteases are involved in de-conjugation under cell stress is unclear. Here, we show that low doses of hydrogen peroxide (H2O2) induce an increase of the SENP3 protein, which removes SUMO2/3 from promyelocytic leukemia (PML). Low dose H2O2 causes SENP3 to co-localize with PML bodies and reduces the number of PML bodies in a SENP3-dependent manner. Furthermore, de-conjuration of SUMO2/3 from PML is responsible for the accelerated cell proliferation caused by low dose H2O2. Knocking down PML promotes basal cell proliferation as expected. This can be reversed by reconstitution with wild-type PML but not its mutant lacking SUMOylation, indicating that only the SUMOylated PML can play an inhibitory role for cell proliferation. Thus, SENP3 appears to be a key mediator in mild oxidative stress-induced cell proliferation via regulation of the SUMOylation status of PML. Furthermore, SENP3 is over-accumulated in a variety of primary human cancers including colon adenocarcinoma in which PML is hypo-SUMOylated. These results reveal an important role of SENP3 and the SUMOylation status of PML in the regulation of cell proliferation under oxidative stress. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a master regulator of mitochondrial biogenesis in response to changes in the cellular environment, physiological or pathological status of mammals. PGC-1α is known to be modified by SUMO (Small Ubiquitin-like Modifier). However, it is not known whether SUMOylation could affect the function of PGC-1α in mitochondrial biogenesis and that how PGC-1α SUMOylation is regulated. In this study, we have identified the role of Sentrin/SUMO-specific protease 1 (SENP1) as a specific SUMO protease to regulate SUMOylation status of PGC-1α. More importantly, we have also found that SENP1 promotes PGC-1α transcription activity, which is essential for the expression of mitochondrial genes and subsequently mitochondrial biogenesis. Thus, we reveal that the SUMOylation of PGC-1α controlled by SENP1 plays an important role in mitochondrial biogenesis and function. [ABSTRACT FROM AUTHOR]