Sumo-Binding Proteins As Effectors And Regulators Of Sumo Modification

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC SUMOs (Small Ubiquitin-related Modifiers) are reversibly conjugated to other proteins in the cell, thereby regulating a wide range of essential functions. Many of the functions regulated by SUMOylation are intimately tied to processes directly relevant to cancer, including maintenance of genome integrity and cell cycle regulation. Studies in the past several years have in fact linked SUMOylation to a variety of human cancers, including leukemia, prostrate, breast, and colon cancers. Thus, developing a fundamental understanding of the signals and factors that regulate SUMOylation, as well as how SUMOylation affects protein function, has the potential to lead to important new insights into cancer development, diagnosis, and treatment. We hypothesize that the three SUMO paralogs expressed in vertebrate cells (SUMO-1, SUMO-2 and SUMO-3), as well as their polymeric forms, represent unique signals recognized by unique proteins. Moreover, we propose that SUMOylation often promotes interactions between modified proteins and downstream factors containing SUMO-interacting motifs (SIMs). To test this hypothesis, we have initiated high throughput studies to identify novel SUMO-1, SUMO-2 and SUMO-2 polymeric chain binding proteins. Using microarray analysis, we identified ∼400 mostly nuclear proteins, many with preferential affinity for specific SUMO paralogs. Among these 400 putative SUMO-binding proteins was a family of zinc finger proteins that we have determined to possess a novel SIM. This family of proteins contains a stretch of unique tandem zinc fingers called MYM (myeloproliferative and mental retardation) domains. Although the exact functions of MYM-type zinc finger domains are not known, proteins containing these domains are linked to myeloproliferative syndromes, X-linked mental retardation, and transcriptional regulation. We have found that the MYM-type zinc finger domains are both necessary and sufficient for SUMO-binding. MYM-type zinc finger domains represent only the second known class of SUMO-binding motifs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2184.