Kato-Udagawa, A. | bioRxiv Science

bioRxiv2023

Arsenic induces two different interaction modes of SUMO with promyelocytic leukemia (PML) proteins.

Promyelocytic leukemia-nuclear bodies (PML-NBs) are dot-like protein assemblies and implicated in the pathogenesis of leukemia and viral infection. PML is the scaffold protein of PML-NB and its client proteins such as SUMO, DAXX, and Sp100 reside in PML-NBs. It is known that a short exposure to trivalent arsenic (As3+) induces the solubility change and the subsequent SUMOylation of PML, and the SUMO interacting motif (SIM) is not necessary for these biochemical changes. However, it has not been well studied how As3+ initiates or enhances the association of SUMO with PML and the other PML-NB client proteins. Here, we report that As3+ enhanced non-covalent association of PML with SUMO via the SUMO-SIM interaction which is dispensable for the solubility change and SUMOylation of PML. We also report that the As3+-induced solubility change of PML was not affected by ML792, a SUMO E1 enzyme inhibitor, even though the nuclear localization of SUMO2/3 and protein SUMOylation were halted by ML792. As3+ did not change the solubility of DAXX and SUMOylation enzymes such as SAE1, UBA2, and UBC9. In contrast, As3+ induced SUMOylation of Sp100 with a concomitant loss of its solubility like PML in human leukemia cell lines. Our current results indicate that both covalent and non-covalent associations of SUMO with PML are increased in As3+-exposed cells, and Sp100 may play a role in the maintenance of PML-NBs.

cell biology↗

bioRxiv2021

Promyelocytic leukemia nuclear body (PML-NB) -free intranuclear milieu facilitates development of oocytes in mice

Promyelocytic leukemia (PML) nuclear bodies (PML-NBs), a class of membrane-less organelles in cells, are involved in multiple biological activities and are present throughout cells of adult organisms. Although the oocyte nucleus is an active region for the flux of multiple non-membranous organelles, PML-NBs have been predicted to be absent from oocytes. Here, we show that the deliberate assembly of PML-NBs during oocyte growth preferentially sequestered Small Ubiquitin-related Modifier (SUMO) protein from the nucleoplasm. SUMO not only was involved in the regulation of oocyte nuclear maturation but also was committed to the response, mediated by liquid droplet formation, to multiple stressors including nucleolar stress and proteotoxic stresses. Exogenous assembly of PML-NBs in the nucleus of oocytes affected the efficiency of the response of SUMO. These observations suggest that the PML-NB-free intranuclear milieu ensures that a reserve of SUMO remains available for emergent responses in oocyte development. This work demonstrated a benefit of the PML-NB-free intranuclear milieu, namely the ability to redirect the flux of SUMO otherwise needed to control PML-NB dynamics.

developmental biology↗