Numerous cellular processes are regulated by the reversible conjugation of ubiquitin (UB) or ubiquitin-like (UBL) proteins to substrates. The human genome encodes several DUBs or deubiquitinating enzymes which oppose the function of E3 ligases. Several keys functions have been attributed to deubiquitinating enzymes:
- Deubiquitination can rescue proteins from degradation
- Deubiquitination can remove a non degradative signal used by cells
- Action together with E3 ligases maintain the normal intracellular pool of ubiquitin.
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Several viruses encode viral deubiquitinases. One of the functions of these viral deubiquitinases is to prevent host innate response activation. For example, EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-kB signaling during viral infection. KSHV ORF64, a protein with deubiquitinase (DUB) activity, suppresses RIG-I-mediated IFN signaling by reducing the ubiquitination of RIG-I, essential for its activation. PLP2 protein from murine hepatitis virus, strongly inhibits cellular type I interferon production.