Proper progression of neurogenesis relies on a defined pattern of SUMO-modified proteins

Neurogenesis is a complex process involving the orchestration of many transcription factors and other proteins. Fine regulation of their activities is crucial for proper progression of neurogenesis. A few decades ago, covalent attachment of Small Ubiquitin-like MOdifier (SUMO) to other proteins was revealed as a major regulator of protein activities, constituting an essential posttranslational modification system in vertebrates. Since then, hundreds of proteins have been shown to be targets of SUMO, which is implicated in controlling many relevant processes in eukaryotic cells. These include the development and function of the nervous system, with SUMO tightly linked to synapsis and to neurodegenerative diseases (Yau et al., 2020). The SUMO protease SENP7 has been involved in neurogenesis (Juárez-Vicente et al., 2016), while sumoylation of BRAF35, a subunit of the LSD1 histone demethylase complex, assures the undifferentiated state of neural progenitors (Ceballos-Chávez et al., 2012). In addition, increased sumoylation in mouse brain-derived neural stem cells results in enhanced neuronal differentiation (Bernstock et al., 2019). However, in general, the implication of SUMO in neuronal differentiation and nervous system development has been poorly studied. We have recently developed a proteomic study aimed at identifying SUMO targets associated either with proliferation or with neuronal differentiation conditions, which has highlighted the relevance of SUMO modification for proper progression of neurogenesis. Here, we discuss our recent results, present specific SUMO targets that are key to the process, and indicate future research directions to uncover the molecular mechanisms underlying SUMO modification of relevant neurogenesis-associated factors.Research at the MGD lab is currently supported by grants PGC2018-094232-B-I00 from the Ministry of Science, Innovation and Universities (MICIU), Spain, and CV20-93141 from the Andalusian regional government (both co-financed by the European Regional Development Fund). We apologize to those authors not cited here due to space limitations