Ubiquitin-specific protease 9x (Usp9x), also known as ubiquitin carboxyl-terminal hydrolase FAF-X or FAM, is a deubiquitinase that acts as an important component in TGF-beta and bone morphogenetic protein signalling. It specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33 []. It is involved in axonal growth and neuronal cell migration []. Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis [].
Ubiquitin-specific peptidase 24 (USP24, MEROPS identifier C19.047) is a de-ubiquitinating enzyme that is associated with late-onset Parkinson's Disease []. The enzyme is known to remove ubiquitin from damage-specific DNA-binding protein 2 (DDB2), increasing its stability. DDB2 is involved in DNA damage recognition in the nucleotide excision repair pathway, and is a component of an E3 ligase that targets XPC, histones and DDB2 itself []. USP24 also de-ubiquitinates p53, and cells are resistant to apoptosis following UV irradiation if USP24 is depleted because p53 is stabilized []. Single-nucleotide polymorphisms of the USP24 gene have been identified in lung cancer malignancy and could be diagnostic markers for the disease []. The USP24 gene is up-regulated when the USP9X gene is down-regulated by shRNA, leading to increased survival of B-cell myeloma cells []. USP24 positively regulates ferritinophagy, a process in which ferritin is degraded in lysosomes and releases free iron [].
