Ubiquitin-Specific Peptidase 18: a Multifaceted Protein Participating in Breast Cancer

ABSTRACT

Mammary tumors display high molecular heterogeneity with regards to their transcriptomes and proteomes. The regulation of several posttranslational modifications, such as ubiquitination and ISGylation, directly influences the proteome of breast cancer cells. In particular, ISGylation is emerging as a critical factor in different cancer types and is particularly relevant in breast cancer. This modification involves the covalent binding of interferon stimulated gene 15 (ISG15) to its target proteins. Interestingly, ubiquitin-specific protease 18 (USP18), also called UBP43, reverses ISGylation. In addition to its activity as a de-ISGylation enzyme, USP18 is also a negative regulator of type I IFN signaling. Several studies indicate a central role of USP18 in the pathogenesis of breast cancer. This chapter discusses recent insights gained in the molecular mechanisms of USP18 in breast cancer, and its potential implications for the development of novel therapeutic strategies for this disease.