Post-translational modifications by ubiquitin-like modifiers (proteins similar to ubiquitin) can influence many aspects of protein homeostasis, such are stability, localization or activity. SUMOylation is a reversible process by which SUMO, the Small Ubiquitin-like Modifier, is attached to target proteins and modify their properties. We discovered that SUMO has an important role in cholesterol intake, contributing to steroid hormone synthesis through the regulation of the Scavenger Receptors SR-B1 and the nuclear receptor Ftz-f1, homologous to the human Steroidogenic Factor 1, SF-1. The regulation of hormonal synthesis is a crucial step that determines animal viability and size. This novel function of SUMOylation is conserved in several tissues in different organisms. To investigate more in detail the function of the ubiquitin-likes, we are developing new molecular tools to isolate and identify proteins modified by SUMO and other Ubiquitin-like modifiers in human cells and in model systems, such is Drosophila. We generated a versatile, highly specific, easy-to-use toolbox composed of vectors useful to analyze the modification of a protein of interest or to identify modified sub-proteomes. Among the transcription factors regulated by SUMOylation, we are interested on the SPALT-Like (SALL) family of proteins, necessary for numerous biological processes. Mutations in SALL1 and SALL4 cause the rare diseases Townes-Brocks and Okihiro (Duane-Radial Ray) Syndromes, respectively, being also involved in the susceptibility to tumors. Patients might present dysplastic kidneys, supernumerary thumbs, malformed ears, sensorineural hearing loss and severe growth retardation. We are investigating the mechanism by which a truncated form of SALL1 causes the Townes-Brocks symptoms. We hypothesized that these are caused by the malfunctioning of primary cilia and we are currently performing the experiments necessary to prove this hypothesis. Primary fibroblasts derived from a Townes-Brocks patient, which exhibit mutation in the gene SALL1. The fibroblasts were kindly provided by Dr. Wilkie, Oxford, UK. Markers: Acetylated tubulin (red), F-actin (green), DNA (blue). Representation of SUMO evolution across species, with associated functional consequences in human, Blattella and Drosophila.
Life & Medical Sciences
- Biosciences & Health
- Biomedically relevant genes and processes