Emerging Role of Ubiquitin-Specific Protease 19 in Oncogenesis and Cancer Development

Abstract

Ubiquitination and ubiquitin-like post-translational modifications control the activity and stability of different tumor suppressors and oncoproteins. Hence, regulation of this enzymatic cascade offers an appealing scenario for novel antineoplastic targets discovery. Among the different families of enzymes that participate in the conjugation of Ubiquitin, deubiquitinating enzymes (DUBs), responsible for removing ubiquitin or ubiquitin-like peptides from substrate proteins, have attracted increasing attention. In this regard, increasing evidence is accumulating suggesting that the modulation of the catalytic activity of DUBs represents an attractive point of therapeutic intervention in cancer treatment. In particular, different lines of research indicate that USP19, a member of the DUBs, plays a role in the control of tumorigenesis and cancer dissemination. This review aims at summarizing the current knowledge of USP19 wide association with the control of several cellular processes in different neoplasms, which highlights the emerging role of USP19 as a previously unrecognized prognosis factor that possesses both positive and negative regulation activities in tumor biology. These observations indicate that USP19 might represent a novel putative pharmacologic target in oncology and underscores the potential of identifying specific modulators to test in clinical settings.

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer

“…USP19 is a kind of deubiquitinating protease. Similar to NCCRP1, USP19 is aberrantly expressed in multiple cancers and may act as a tumour suppressor gene or oncogene, which relies upon the tumour type (Rossi and Rossi, 2022). For example, USP19 was found to be upregulated in TNBC tissues and promote the invasion and metastasis of TNBC (Rossi et al, 2021).…”

Ubiquitin-modifying enzymes in Huntington’s disease

“…The other isoform contains a relatively hydrophilic region and an EEVD motif in the C-terminus and has a cytoplasmic localization. USP19 plays a role in the protein quality control system, protein homeostasis, muscle development, tumorigenesis and controls the half-life of several proteins (Rossi and Rossi, 2022). Overexpression of cytoplasmic localized isoform of USP19 in mHTT-expressing cells increased mHTT levels and aggregation.…”

Targeting sterol-O-acyltransferase 1 to disrupt cholesterol metabolism for cancer therapy

“…Studies have shown that P53 can not only directly regulate the mRNA levels of SOAT1 involved in cholesterol metabolism but can also regulate the protein levels of SOAT1 by regulating the mRNA levels of USP19 ( 39 ). Ubiquitin-specific peptidase 19 (USP19) is a deubiquitinating enzyme (DUB) that stabilizes SOAT1 by decreasing its ubiquitination ( 42 ). Potential ubiquitination of SOAT1 includes the ϵ-amino groups of the protein’s seven lysine residues (K6, K11, K27, K29, K33, K48, and K63).…”