Mutations in the NF-κB signaling pathway: implications for human disease

NF-κB and the immune response

“…The centrality of its antiapoptotic function is supported in part by the demonstration that most of the requirements for NF-kB during T-cell development can be overcome by transgenic expression of the prototypical antiapoptotic factor Bcl-2 (Sentman et al, 1991). The necessity of NF-kB for lymphopoiesis is strikingly illustrated in human genetic diseases wherein the gene encoding NEMO is inactivated by mutation (see Courtois and Gilmore, 2006). Because the NEMO gene is located on the X-chromosome, it is usually subject to random inactivation in individual cells in females.…”

Nuclear factor-κB and inhibitor of κB kinase pathways in oncogenic initiation and progression

“…Subsequently, it was shown that the NF-kB p52/p100 subunit encoded by the NFKB2 gene undergoes structural alterations in certain T-cell lymphomas, chronic lymphocytic leukemias, myelomas and B-cell lymphomas (see Courtois and Gilmore, 2006). Similarly, the gene for the IkB family member Bcl-3 is found to be translocated and overexpressed in some B-cell leukemias.…”

“…Similarly, the gene for the IkB family member Bcl-3 is found to be translocated and overexpressed in some B-cell leukemias. In addition, c-rel gene amplification is detected in several types of B-cell lymphoma, whereas a subset of Hodgkin's lymphoma cases contain IkBa gene mutations or deletions (Orlowski and Baldwin, 2002;Courtois and Gilmore, 2006).…”

Inhibitors of NF-κB signaling: 785 and counting

“…Interestingly, several truncated p100 proteins, which would lack key proteasomal processing signals and could act as p100-SRs, are created by chromosomal alterations in leukemias/lymphomas (see Courtois and Gilmore, 2006).…”