Targeting the ubiquitin system for treatment of cilia-related diseases

Abstract

The ubiquitin system regulates a wide variety of cellular functions. Not surprisingly, dysregulation of the ubiquitin system is associated with various disorders. Therefore, drugs that can modulate the functions of the ubiquitin system have been actively developed to treat these disorders. Chemical knockdown of pathogenic proteins using the ubiquitin-proteasome system is also a promising approach. The ubiquitin system regulates the assemble and disassemble of primary cilia through balanced control over the ubiquitination and deubiquitination of ciliary proteins. Primary cilia are antenna-like structures present in many vertebrate cells that sense and transduce extracellular cues to control cellular processes such as proliferation and differentiation. Impairment of primary cilia is associated with many diseases, including cancer and ciliopathy, a group of multisystem developmental disorders. In this review, we focus on the role of the ubiquitin system on cilia-related disorders and discuss the possibility of the ubiquitin system as therapeutic targets for these diseases through regulation of primary cilia formation.