USP15, which is highly similar with USP4 , also is involved in Wnt signaling and bone formation .
USP15, which regulates osteoblast function and bone formation, is connected to osteoclast function too .
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).
Gonzalez-Junca et al., "USP15 stabilizes TGF-[beta] receptor I and promotes oncogenesis through the activation of TGF-[beta] signaling in glioblastoma," Nature Medicine, vol.
Dingwell et al., "USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling," Open Biology, vol.
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.
Joan Seoane , Director of Translational Research at the Vall d'Hebron Institute of Oncology (VHIO) and ICREA Research Professor identified USP15 as a critical protein in cancer which, thanks to its molecular characteristics, shows enormous therapeutic promise.
USP15 promotes tumor progression by activating the TGFa pathway.
Seoane's team has unmasked the USP15 enzyme as activator of the TGFa chain reaction.
USP15 acts by controlling and correcting the TGFa activity in the same way that a thermostat regulates temperature.