Figure 3 ,Table 1个

    • Figure 1.  Met1-Ub system. A Schematic diagram of the LUBAC subunits, HOIP, HOIL-1L and SHARPIN. Arrows indicate interactions. B The model that LUBAC conjugates Met1-Ub to the substrate. E1 activates ubiquitin and leads to the formation of a thioester bond between the C terminus of ubiquitin and the catalytic cysteine of E1 (E1~Ub). Then the activated ubiquitin is transferred to the catalytic cysteine of E2 to form the E2~Ub thioester intermediate. Concomitantly, LUBAC binds E2~Ub and substrate to facilitate the transfer of ubiquitin molecules to the substrate. Arrows indicate the transfer of ubiquitin molecular. C Schematic diagram of LUBAC-associated DUBs, OTULIN and CYLD-SPATA2. Arrows indicate interactions. PUB, peptide:N-glycanase/ubiquitin-associated UBA-containing or UBX-containing protein; ZF, zinc finger; NZF, Npl4-like zinc finger; UBA, ubiquitin-associated; RING, really interesting new gene; IBR, in-between-RING; LDD, linear ubiquitin chain-determining domain; PH, pleckstrin homology; LTM, LUBAC-tethering motif; UBL, ubiquitin-like; PIM, PUB-interacting motif; OTU, ovarian tumour; CAP-Gly, cytoskeleton-associated protein glycine-rich; USP, Ubiquitin specific protease; B-box, B-box type zinc finger

    • Figure 2.  Functions of Met1-Ub in cell signaling. Various upstream stimuli lead to multiple regulation events that activate LUBAC. Then, LUBAC conjugates Met1-Ub on downstream substrates that are involved in the regulation of diverse cellular functions. The cell signaling regulated by Met1-Ub and a partial list of known substrates is shown at the bottom

    • Figure 3.  Met1-Ub plays a central role in TNF-induced NF-кB signaling and cell death. TNF stimulation triggers the recruitment of LUBAC to complex-I where it mediates the Met1-Ub of NEMO and other components of TNF-RSC. Met1-Ub of NEMO activates IKK and subsequent NF-кB signaling. Met1-Ub of the components of TNF-RSC prevents the formation of complex-II, thereby suppressing TNF-induced cell death, apoptosis and necroptosis. DUBs such as OTULIN and CYLD antagonize the actions of LUBAC by restricting the accumulation of Met1-Ub. LUBAC recruitment also ensures the full activation of the MAPK pathway. Different ubiquitin linkage types are indicated in the figure