SUMO-1 is a ubiquitin-like protein. SUMO-1 can be covalently conjugated to other proteins through an isopeptide linkage in a manner similar to ubiquitin. A number of SUMO-1 conjugation substrates have been reported in vertebrates to date; these include RanGAP1, RanBP2, PML, Sp100, IkBa, HIPK2, p53, topoisomerase I, c-Jun and the Werner's Syndrome gene product. Western blotting analysis suggests that the reported SUMO-1 substrates are a subset of the total number of cellular proteins that are conjugated to SUMO-1 in vivo. The SUMO-1 conjugation pathway utilizes enzymes that show both sequence similarity and structural conservation with ubiquitin activating (E1) and conjugating (E2) enzymes. Moreover, biochemical analysis suggests that ubiquitin and SUMO-1 enzymes carry out their functions using similar enzymatic mechanisms. However, none of the enzymes characterized to date act in both the ubiquitin and SUMO-1 conjugation pathways. We are studying the SUMO-1 pathway in vertebrates. We are particularly interested in the regulation of this pathway during the cell cycle and its role in controlling the Ran GTPase activating protein RanGAP1 through conjugation. Our goals are to understand this pathway and its regulation at a molecular level, to determine whether and how it regulates mitosis in vertebrates. Toward this goal, we have analyzed the localization, abundance and behavior of enzymes involved in SUMO-1 conjugation and deconjugation, as well as the disruption of this pathway in disease states (acute promyelocytic leukemia) and through the action of viral proteins (HSV-1 ICP0).
| Dasso, Mary (2016) Kar9 Controls the Cytoplasm by Visiting the Nucleus. Dev Cell 36:360-1 |
| Chow, Kin-Hoe; Elgort, Suzanne; Dasso, Mary et al. (2014) The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function. Mol Biol Cell 25:160-8 |
| Ryu, Hyunju; Gygi, Steven P; Azuma, Yoshiaki et al. (2014) SUMOylation of Psmd1 controls Adrm1 interaction with the proteasome. Cell Rep 7:1842-8 |
| Chow, Kin-Hoe; Elgort, Suzanne; Dasso, Mary et al. (2012) Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2. Nucleus 3:349-58 |
| Mukhopadhyay, Debaditya; Arnaoutov, Alexei; Dasso, Mary (2010) The SUMO protease SENP6 is essential for inner kinetochore assembly. J Cell Biol 188:681-92 |
| Wang, Yonggang; Dasso, Mary (2009) SUMOylation and deSUMOylation at a glance. J Cell Sci 122:4249-52 |
| Mukhopadhyay, Debaditya; Dasso, Mary (2007) Modification in reverse: the SUMO proteases. Trends Biochem Sci 32:286-95 |
| Mukhopadhyay, Debaditya; Ayaydin, Ferhan; Kolli, Nagamalleswari et al. (2006) SUSP1 antagonizes formation of highly SUMO2/3-conjugated species. J Cell Biol 174:939-49 |
| Quimby, B B; Yong-Gonzalez, V; Anan, T et al. (2006) The promyelocytic leukemia protein stimulates SUMO conjugation in yeast. Oncogene 25:2999-3005 |
| Azuma, Yoshiaki; Arnaoutov, Alexei; Anan, Tadashi et al. (2005) PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. EMBO J 24:2172-82 |
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