To date, several DUBs are found to regulate osteoblast function (USP4, USP7, USP9x, USP15, UCH-l3, and MYSM1) and osteoclast function (CYLD, USP15, USP18, A20, and POH1) (Table 2).
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Song et al., "Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis," The Journal of Clinical Investigation, vol.
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dUb Target Ubiquitin-mediated Biological molecules modifications function A20 RIP1, RIP2, TRAF2, K63 Signaling TRAF6, MALT1, NEMO termination CYLD MyD88, TRAF2, K63 Signaling TRAF6, TRAF7, termination RIP1, NEMO USP2[alpha] TRAF6 K63 Signaling termination USP4 TRAF2, TRAF6, TAK1 K63 Signaling termination USP7 TRAF6, NEMO K63 Signaling termination USP10 TRAF6, NEMO K63/M1 Signaling termination USP11 IxBa K48 Proteolytic degradation USP15 IxBa K48 Proteolytic degradation USP18 TAK1, NEMO K63 Signaling termination USP21 RIP1 K63 Signaling termination USP25 TRAF2, TRAF3, K63/K48 Signaling TRAF5, TRAF6 termination/ proteolytic degradation Table 4: TLR expression profile.
Data presented in the research article entitled Activity-Based Chemical Proteomics Accelerates Inhibitor Development for Deubiquitylating Enzymes (Chemistry & Biology, Volume 18, Issue 11, 1401-1412, 23 November 2011) confirms the selective inhibition of USP7
in human cells treated with P022077, contrary to the pan-DUB inhibition profile of the tool compound PR-619 in the same cells.