| |  |
| |
| Description | The human nfkb2 gene encodes a protein composed 900 amino acids with an approximately molecular weight of 100 kDa, which was considered as a precursor of p52 subunit of NF-kB complexes. The structural characteristics of NF-kB2 are much similar with that of NF-kB1: A N-terminal RHD; two nuclear localization sequences within the C-terminus of RHD, a putative GRR region that possibly contributes to the generation of NF-kB p52 from the precursor, NF-kB2. The C-terminal region of NF-kB2 also contains multiple copies of the so-called ankyrin repeats and one proline, glutamic acid, serine, and threonine (PEST) domain. Studies demonstrated that NF-kB2 was posttranslationally cleaved to produce the p52 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal 406-900 portion of NF-kB2. However, other studies revealed that the mechanism for the generation of NF-kB p52 is through cotranslational processing. Recent studies demonstrated that the processing of NF-kB p52 required IKKa- and/or NIK-dependent C-terminal phosphorylation of NF-kB2. |
| Expression | nfkb2 is expressed mainly in lymphoid cells and mononuclear cells. |
| Localisation | cytosol, nuclei after activation. |
| Function | regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, and initiation or acceleration of tumorigenesis. Similar with NF-kB1, the full length of NF-kB2 can serve as an endogenous inhibitor for the NF-kB p50/ p65(RelA) or NF-kB p52/p65 heterodimer. The homodimer of NF-kB p52 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p52 homodimer may function to competitively inhibit B binding by transactivating NF- B dimers. The Bcl3 protein can form a complex with this homodimer at B sites and act as a transactivator of NF-kB p52 homodimer. Interaction with : members of IkB family and Rel family, Bcl3. |
| Entity | hematological malignancies (see below) and other diseases: autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, cancer, HTLV-1 infection, and AIDS. |
| Disease | t(10;14)(q24;q11) or t(10;14)(q24;q32) in hematological malignancies |
| Cytogenetics | poor. |
| Oncogenesis | Unlike its relative nfkb1, rearrangement of nfkb2 gene locus has been found in many forms of lymophomas. The chromosomal translocations by t(10;14)(q24;q11) and t(10;14)(q24;q32) cause deletions of sequences encoding the ankyrin repeat motif of NF-kB2. Consequently, this carboxyl terminal truncated NF-kB2 is constitutively located in the nucleus of cells, which was found in small percentage of B-cell non-Hodgkin's lymphoma, cutaneous lymphomas, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemias, and multiple myelomas. Chromosomal translocation generated a fusion NF-kB2- IGHA1 or NF-kB2- TCRa or TCRd transcriptional unit. |
| | |
| B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. |
| Neri A, Chang CC, Lombardi L, Salina M, Corradini P, Maiolo AT, Chaganti RS, Dalla-Favera R |
| Cell. 1991 ; 67 (6) : 1075-1087. |
| PMID 1760839 |
| |
| Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. |
| Liptay S, Schmid RM, Perkins ND, Meltzer P, Altherr MR, McPherson JD, Wasmuth JJ, Nabel GJ |
| Genomics. 1992 ; 13 (2) : 287-292. |
| PMID 1612589 |
| |
| The NF-kappa B and I kappa B proteins: new discoveries and insights. |
| Baldwin AS Jr |
| Annual review of immunology. 1996 ; 14 : 649-683. |
| PMID 8717528 |
| |
| NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. |
| Ghosh S, May MJ, Kopp EB |
| Annual review of immunology. 1998 ; 16 : 225-260. |
| PMID 9597130 |
| |
| New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. |
| Chen F, Castranova V, Shi X, Demers LM |
| Clinical chemistry. 1999 ; 45 (1) : 7-17. |
| PMID 9895331 |
| |
| The generation of nfkb2 p52: mechanism and efficiency. |
| Heusch M, Lin L, Geleziunas R, Greene WC |
| Oncogene. 1999 ; 18 (46) : 6201-6208. |
| PMID 10597218 |
| |
| Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. |
| Senftleben U, Cao Y, Xiao G, Greten FR, Krˆ§hn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M |
| Science (New York, N.Y.). 2001 ; 293 (5534) : 1495-1499. |
| PMID 11520989 |
| |
| Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha. |
| Xiao G, Cvijic ME, Fong A, Harhaj EW, Uhlik MT, Waterfield M, Sun SC |
| The EMBO journal. 2001 ; 20 (23) : 6805-6815. |
| PMID 11726516 |
| |