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.
Keywords: SAE1/SAE2, Ubc9, SUMO E3, Hsp27, SUMO, SUMOpeptidases, SUMO interaction motif (SIM).
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