Role of Sumoylation in modulation of STRA13 and SHARP-1 transcriptional activities and biological functions

Abstract

Abstract of Thesis Post-translational modification of transcription factors by small ubiquitin-like modifiers (SUMO) has emerges as an important mechanism to achieve dynamic regulation of their biological functions. Like ubiquitination, the covalent attachment of SUMO to substrates is through the activities of an enzyme cascade. Despite the similarity in the pathway, the functional consequences of these two modifications are quite different. Unlike ubiquitination which primarily facilitates the target proteins for degradation, sumoylation has diverse effects on substrates. Transcription factors are the largest group of target proteins whose functions are modified by sumoylation. Stra13 and Sharp-1 are basic helix-loop-helix (bHLH) transcription factors expressed in many cell types during embryonic development as well as in adult tissues. They are involved in various biological functions. However, the mechanisms by which their functions are regulated remain unclear. In this study, we provide evidence that sumoylation is required for both Stra13 and Sharp-1 to act as transcriptional repressors. SUMO modification does not alter the sub-cellular localization of both proteins, however, it is essential for Stra13 and Sharp-1 to mediate cell growth arrest, senescence and inhibit skeletal muscle differentiation. Our results reveal new insights into the key roles of SUMO modification into regulation of the biological functions of Stra13 and Sharp-1.