Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity.

ABSTRACT:

Background

Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo.

Methods

In this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models.

Res

SUBMITTER: Pinto-Fernandez A 

PROVIDER: S-EPMC7884788 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature