īorden K, Lally J, Martin S, O’Reilly N, Solomon E, Freemont P (1996) In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML. īaczyk D, Audette M, Drewlo S, Levytska K, Kingdom J (2017) SUMO-4: a novel functional candidate in the human placental protein SUMOylation machinery. Īu W, Tam S, Fong B, Kwong Y (2008) Determinants of cerebrospinal fluid arsenic concentration in patients with acute promyelocytic leukemia on oral arsenic trioxide therapy. Collectively, SUMOylation regulates PML-NBs and As 3+ restricts SUMO dynamics on PML by changing its solubility.Īlkuraya F, Saadi I, Lund J, Turbe-Doan A, Morton C, Maas R (2006) SUMO1 haploinsufficiency leads to cleft lip and palate. Co-localization and further restriction of SUMO2/3 to PML-NBs were confirmed by PML-transfected CHO-K1 cells. Proteasome inhibitors did not change the As 3+-induced SUMOylation levels of PML. TAK243, a ubiquitin E1 inhibitor, did not change the PML-NBs, while SUMOylated proteins accumulated in the TAK243-exposed cells. ML792, a SUMO E1 inhibitor, decreased the number of PML-NBs and reciprocally increased the size irrespective of exposure to As 3+, which itself slightly decrease both the number and size of PML-NBs. Undifferentiated and differentiated THP-1 cells responded to As 3+ similarly and PML proteins were changed from the detergent soluble to the insoluble form and further SUMOylated with SUMO2/3 and SUMO1. In the present study, we report that (1) the number and size of PML-NBs were regulated by SUMO E1-activating enzyme, (2) SUMO2/3 co-localized with PML irrespective of As 3+ exposure and was restricted to PML-nuclear bodies (PML-NBs) via covalent binding in response to As 3+, and (3) As 3+-induced biochemical changes in PML were not modulated by ubiquitin–proteasome system (UPS) in THP-1 cells. However, effects of As 3+ on SUMO dynamics on PML-NBs are not well investigated. PML proteins are rapidly modified both with SUMO2/3 and SUMO1 after exposure to arsenite (As 3+) and SUMOylated PML are further ubiquitinated and degraded by proteasomes.

Promyelocytic leukemia (PML) proteins are good substrates for SUMOylation, and PML-nuclear bodies (PML-NBs) may function as a platform for the PML SUMOylation. The functional roles of protein modification by small ubiquitin-like modifier (SUMO) proteins are not well understood compared to ubiquitination.

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