title: SUMOylation Modulates CFTR Biogenesis: Is the Pathway Druggable?
abstract: The SUMOylation pathway is involved in the regulation of numerous and diverse cellular functions, nuclear as well as extra-nuclear. Thus, it is not surprising that SUMO pathway components are implicated in diseases as diverse as cystic fibrosis, cancer and neurodegenerative diseases. Therefore, the components of the SUMOylation pathway should provide valid therapeutic targets for manipulation. While the related ubiquitylation system encompasses a vast number of enzymes as potential drug targets, there are only a handful of components that comprise the SUMOylation cascade. Whereas this alleviates the problem of target redundancy, it may complicate the potential to achieve drug specificity. The development of small molecule inhibitors aimed at SUMO pathway components is in its early stages. This review provides an outline of the pathway and summarizes drug development efforts targeted at individual SUMOylation pathway components, with an emphasis on how CFTR protein processing may be affected.
authors.forename: Annette
authors.initials: A
authors.lastname: Ahner
authors.affiliation: University of Pittsburgh School of Medicine, Department of Cell Biology, 7116 Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. frizzell@pitt.edu.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Frizzell
mesh_terms: D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation / Q000187:drug effects*
chemical_list: D054852:Small Molecule Libraries; D025841:Small Ubiquitin-Related Modifier Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator