Ubiquitin-specific peptidase 42 (USP42)

Ubiquitin-specific peptidase 42 (USP42) is a cysteine-type deubiquitinating enzyme involved in the removal of ubiquitin from protein substrates, thereby regulating protein stability and degradation. USP42 interacts directly with p53 and is required for rapid activation of p53-dependent transcription and cell-cycle arrest in response to cellular stress, which contributes to cellular recovery after mild or transient damage. USP42 also governs the formation and function of nuclear speckles, influencing mRNA splicing through phase separation dynamics. Overexpression of USP42 is associated with cancer progression, including increased proliferation, invasion, and poor prognosis in gastric and lung cancers. As a result, USP42 is considered a novel therapeutic target in oncology for modulation of protein stability and cellular stress responses.

Other names

Ubiquitin carboxyl-terminal hydrolase 42Deubiquitinating enzyme 42Ubiquitin thioesterase 42Ubiquitin-specific-processing protease 42FLJ12697USP42Ubiquitin specific protease 42Ubiquitin thiolesterase 42

Inhibition of USP42's deubiquitylase activity would prevent removal of ubiquitin from substrates (e.g., p53), leading to altered protein stability and increased degradation of key regulatory proteins. Targeting USP42 may affect phase separation of nuclear speckles and mRNA splicing, hence interfering with processes essential for cancer cell growth.