IndraLab

"First, CYLD inhibits NF- κ B signaling by deubiquitinating NF- κ B-positive regulators, such as TAK1 (TGF- β -activated Kinase 1), TRAF2 and NEMO/IKK γ . xref , xref Second, caspase 8-mediated cleavage of CYLD generates a survival signal, whereas the mutation of caspase 8-mediated cleavage site on CYLD switches cell survival to necrotic cell death in response to TNF α . xref Last but not least, CYLD interacts with and deubiquitinates RIP1. xref However, it is still controversial whether CYLD affects the ubiquitination of RIP1 in complex I or in the necrosome. xref , xref Given that the above DUBs can remove ubiquitin chains from RIP1, how is RIP1 ubiquitinated?"

"It was demonstrated by a biochemical study that CYLD has an ability to cleave not only Lys 63-linked ubiquitin chains, but also linear ubiquitin chains ( xref ), which discovery was followed up by a cellular signaling study showing that CYLD inhibits the NF-κB signaling by forming a complex with LUBAC ( xref )."

"Using an shRNA approach, Brummelkamp et al. showed that CYLD inhibits NF-κB signaling by counteracting TRAF2 ubiquitination [ xref ]."

"It is possible that fibulin-3 downregulation increases CYLD that in turn inhibits NF-κB signaling, but the mechanisms by which fibulin-3 regulates CYLD at the transcriptional level is yet unknown."

"Furthermore, EAC also inhibited the cell survival signaling by enhancing the amount of IkappaBalpha in cytoplasm and reducing the level and activity of NF-kappaB in the nucleus, and subsequently attenuated the expression of Bcl-X(L) in Hep G2 and PLC/PRF/5 cells."

"The deubiquitylating enzyme CYLD additionally inhibits TGF-β signaling by forming a complex with Smad7 and facilitates its deubiquitylation at two sites in its MH2 domain ( xref )."

"CYLD inhibits RANK-mediated signaling in osteoclasts in a negative feedback loop by deubiquitinating TRAF6 ( xref ) ( xref )."

"It was initially believed that CYLD inhibited IFN signaling by deubiquitinating the PRR, RIG‐1, and downstream kinases TANK‐binding kinase 1 (TBK‐1) and inhibitor of NF‐κB kinase Ε (IKKΕ) xref ; but, surprisingly, IFN response to vesicular stomatitis virus in CYLD knockout mice or cells from these mice was abrogated. xref On the basis of these reports, TRAF3 and CYLD may serve similar functions after viral infection, namely, to inhibit NF‐κB and activate IFN."

"In the Wnt signal transduction pathway, CYLD inhibits β-catenin signaling by removing Lysine-63 linked ubiquitination from Dishevelled (Tauriello et al., xref )."

"Finally, the deubiquitylase CYLD inhibits TGF-β signaling by decreasing the stability of Smad3."

"Furthermore, EAC also inhibited the cell survival signaling by enhancing the amount of I κ - α in cytoplasm and reducing the level and activity of nuclear factor (NF)- κ B in the nucleus, and subsequently attenuated the expression of Bcl-X L in Hep G2 and PLC/PRF/5 cells [ xref ]."

"Like A20, CYLD inhibits signaling by disassembling the K63 polyubiquitin recruiting signal."

"It has been demonstrated that the deubiquitinating enzymes A20 and CYLD inhibit NF-κB signaling by targeting TRAF6 upstream of IKK ( xref ; xref ; xref ; xref ), while the deubiquitinating protein DUBA inhibits type I interferon activity by targeting TRAF3 ( xref )."

"CYLD inhibits RANK signaling by deubiquitinating TRAF6, and CYLD requires the adaptor molecule p62 to interact with TRAF6 [ xref ]."