Expression of LIMD1 is absent or decreased in many cancers including breast cancer, lung carcinoma and blood cancers. LIMD1 is an adapter Oxolinic acid protein that is involved in the assembly of numerous protein complexes such as Rb and TRAF6, and participates in several cellular processes such as repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. LIMD1 also positively regulates microRNA -mediated gene silencing by binding to the core proteins of the microRNA induced silencing complex such as Ago1/2. To verify the correlation between IRF4 and LIMD1, a panel of EBV-negative and -positive B cell lines derived from B lymphomas or transformed with EBV in vitro were subjected to immunoblotting analysis with IRF4- and LIMD1-Naftidrofuryl oxalate specific antibodies. As shown CFLAR encodes c-FLIP, a master inhibitor of Fas/TRAIL/ TNFa-induced apoptosis. Resistance to Fas/TRAIL-mediated apoptosis is a common mechanism used by tumors to evade the immune system. Similar to LIMD1, CFLAR expression is high in type 3 latency, but was not detected in EBV-negative B cells and EBV type I latency. Furthermore, depletion of IRF4 in JiJoye cells decreases endogenous CFLAR protein level. However, depletion of IRF4 did not affect the protein level of LIMD1, suggesting that LIMD1 and IRF4 are both upregulated by a common transcription factor rather than LIMD1 is a direct target for IRF4. These results confirm that IRF4 is correlated with LIMD1 and CFLAR in B lymphomas, and strongly suggest that CFLAR is a transcriptional target for IRF4. Because these two cell lines have different genetic background, only a small portion of overlapping genes were identified between these two cell lines, with 54 in the upregulated gene group and 14 in the downregulated gene group. This observation is consistent with the fact that IRF4 is a quintessential ����contextdependent���� factor which regulates distinct groups of targets in different contexts. Among the overlapping target genes between JiJoye and IB4, we confirmed the regulation of IFI27, IFI44, IFIT1, GBP1, CD88, CXCL10, and ARHGAP18 by IRF4 using real-time PCR with specific primers.
LIMD1 is an adapter protein is involved in the assembly of numerous protein
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