IndraLab

Statements


| 31

sparser
"Interestingly, a F312A mutation in human NEMO, which corresponds to the F305A mutation in mouse NEMO tested in this study, was shown to be defective in binding to Lys63-linked ubiqutin chains xref , which suggests that K13 activates NF-κB independent of Lys63-linked chains as well."

sparser
"Ectopic expression of K13 failed to induce nuclear p65/RelA DNA binding activity in theNEMO −/Y MEFs reconstituted with an empty vector, but resulted in approximately 3 fold increase in the nuclear p65/RelA DNA binding activity in those reconstituted with the wild-type NEMO, thereby confirming that NEMO is required for K13-induced NF-κB activation ( xref )."

sparser
"The stimulatory effect of 4OHT on G 1 to S phase transition was blocked by treatment with Bay-11-7082, thereby confirming the role of K13-induced NF-κB activation in this process ( xref )."

sparser
"The K13-TRAF2 interaction is believed to be essential for the recruitment of K13 to the I-kappaB kinase (IKK) complex and for K13-induced NF-kappaB and JNK activation."

sparser
"Thus, binding of NEMO to linear polyubiquitin chain is not required for K13-induced NF-κB activation."

sparser
"HOIL-1 is not Essential for K13-induced NF-κB Activation."

sparser
"Selective NF-kappaB activation by K13 might represent a novel strategy employed by the virus to promote latency."

sparser
"Biochemical studies have revealed some insights into the molecular mechanisms that control NF-κB activation by K13 and K15."

sparser
"TRAF6 is not Required for K13-induced NF-κB Activation."

sparser
"As shown in xref , treatment with 4OHT resulted in equivalent upregulation of A20 in theTRAF6 +/+ andTRAF6 −/− ,which argues against the involvement of TRAF6 in K13-induced NF-κB activation."

sparser
"Based on the lack of involvement of TRAF6, TAK1 and LUBAC in K13-induced NF-κB activation, we support a model according to which the interaction between K13 and NEMO is direct and is not mediated via the TRAF family members or the linear ubiquitin chains."

sparser
"Selective inhibitors of the IKK1 kinase activity may have a role in the treatment of disorders caused by abnormal NF-kappaB activation by HHV8 vFLIP K13."

sparser
"Our results withHOIL-1 − / − and cpdm MEFs, rule out the requirement of LUBAC-induced linear polyubiquitination in K13-induced NF-κB activation."

sparser
"We used HOIL-1 -null MEFs to test the involvement of LUBAC-induced linear polyubiquitination in K13-induced NF-κB activation."

sparser
"The studies in the preceding section clearly demonstrate that TAK1, TRAF6 and linear polyubiquitination of NEMO are not involved in K13-induced NF-κB activation."

sparser
"K13-induced NF-κB activation has been reported to play an essential role in promoting the survival of latently-infected PEL cells by up-regulating the expression of anti-apoptotic proteins xref ."

sparser
"TAK1 is not Required for K13-induced NF-κB Activation."

sparser
"Furthermore, endogenously expressed TRAF2 and TRAF3 do not interact with K13 and play no role in K13-induced NF-kappaB activation or its interaction with the IKK complex."

sparser
"Despite this fact, alteration of these residues in K13 results in a mutant K13 that no longer activates NF-κB ( xref )."

sparser
"To study the role of TAK1 in K13-induced NF-κB activation, we took advantage of murine embryonic fibroblast (MEFs) cells deficient in this protein."

sparser
"In this study, we have investigated the role of TRAF6, TAK1 and LUBAC in K13-induced NF-κB activation."

sparser
"To confirm the lack of involvement of linear polyubiquitination in K13-induced NF-κB activation, we took advantage of cells that are deficient in two essential components of LUBAC, an enzyme complex required for linear polyubiquitination."

sparser
"In addition, TRAF3 has been reported to be required for K13-induced NF-kappaB and JNK activation."

sparser
"Therefore, we believe that rather than blocking NF-κB pathway globally, the ideal agent for the treatment of KSHV-associated lymphoproliferative disorders should selectively block K13-induced NF-κB activation."

sparser
"As another independent test to rule out the involvement of linear Ub chains in K13-induced NF-κB activation, we tested the ability of CYLD to block K13-induced NF-κB-Luc reporter activity."

sparser
"Sharpin is not Essential for K13-induced NF-κB Activation."

sparser
"The lack of requirement of linear polyubiquitination in K13-induced NF-κB activation was further supported by our results showing that CYLD, a deubiquitylating enzyme that can cleave linear ubiquitin chains, cannot block K13-induced NF-κB activity."

sparser
"In this report, we have excluded the involvement of TRAF6, which has been implicated in NF-κB activation during signaling emanating from IL-1 and Toll like receptors xref , xref , in K13-induced NF-κB activation."

sparser
"Furthermore, linear polyubiquitination of NEMO is not required for K13-induced NF-κB activation."

sparser
"Taken collectively with previous studies, the above results confirm that TAK1 is not required for K13-induced NF-κB activation."

sparser
"Thus, K13 activates NF-κB via a mechanism distinct from that utilized by inflammatory cytokines."