USP10
Description
The USP10 (ubiquitin specific peptidase 10) is a protein-coding gene located on chromosome 16.
Ubiquitin specific peptidase 10, also known as USP10, is an enzyme which in humans is encoded by the USP10 gene.
== Function == Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene.
== Interactions == USP10 has been shown to interact with G3BP1. In the endothelium, USP10 regulates Notch signaling by slowing down the degradation of the intracellular domain of NOTCH1.
USP10 (Ubiquitin specific peptidase 10) is a deubiquitinase that removes ubiquitin from a variety of target proteins, influencing various cellular processes. USP10 stabilizes p53 by deubiquitinating it, both in the cytoplasm and nucleus, counteracting the action of MDM2, a p53 degradation regulator. This impacts DNA damage response pathways. USP10 also regulates autophagy by stabilizing BECN1, a key autophagy regulator, through deubiquitination. This interaction creates a feedback loop where PIK3C3/VPS34 complexes, in turn, regulate USP10 stability, influencing p53 levels. Notably, USP10 does not deubiquitinate MDM2. USP10 is critical for 40S ribosome subunit recycling during stalled translation. It inhibits stress granule formation by reducing the activity of G3BP1 and G3BP2, which are involved in stress granule assembly. Furthermore, USP10 directly deubiquitinates 40S ribosomal proteins, including RPS2, RPS3, and RPS10, preventing their degradation and promoting ribosome recycling. This contributes to ribosome quality control during translation initiation. USP10 also deubiquitinates CFTR in early endosomes, enhancing its recycling. USP10 participates in a negative feedback loop to attenuate NF-kappa-B activation by deubiquitinating IKBKG or TRAF6 in response to IL1B stimulation or DNA damage. It deubiquitinates TBX21, stabilizing it. Interestingly, USP10 negatively regulates the RLR signaling pathway during RNA virus infection by removing polyubiquitin chains from MAVS, inhibiting its aggregation and activation. USP10 forms a complex with TANK, ZC3H12A, and itself, which inhibits NF-kappa-B activation by promoting deubiquitination of IKBKG and TRAF6. USP10 interacts with IKBKG, TANK, TRAF6, and ZC3H12A, and these interactions are enhanced by DNA damage. It also interacts with G3BP1 and G3BP2 through its NTF2 domain, inhibiting stress granule formation. {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}
USP10 is also known as UBPO.
