| Description | The nfkb1 gene encodes a protein composed 968 amino acids with an approximately molecular weight of 105 kDa, which was considered as a precursor of p50 subunit of NF-kB complexes. In the N-terminal region of NF-kB1, there is a Rel homology domain (RHD) composed of ~300 amino acids that are responsible for DNA binding, dimerization with other Rel family members, and interaction with IkB proteins. The C-terminal region of NF-kB1 contains multiple copies of the so-called ankyrin repeats which is found in IkB family members, including IkBa, IkBb, IkBe, Bcl3, and Drosophila cactus. The earlier studies by several groups demonstrated that NF-kB1 was posttranslationally cleaved to produce the p50 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal portion of NF-kB1. Further studies by Lin and Ghosh suggested that a glycine-rich region (GRR) within the region of 375 to 400 of NF-kB1 is necessary and sufficient for directing the cleavage of NF-kB1. However, recent studies challenged this model and revealed a novel mechanism in which p50 is generated by a unique cotranslational processing event involving the 26S proteasome. In other words, NF-kB1 is not the precursor of p50. |
| Expression | nfkb1 is widely expressed in virtually all type of cells in both adults and in the embryo. |
| 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. The full length of NF-kB1 can serve as an endogenous inhibitor for the NF-kB p50/p65(RelA) heterodimer. It has been proposed that the homodimer of NF-kB p50 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p50 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 p50 homodimer. Interaction with : members of IkB family and Rel family, LYL1 , Bcl3, NCOA1a(V). |
| Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. |
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| PMID 1612589 |
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| PMID 9597130 |
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| Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome. |
| Lin L, DeMartino GN, Greene WC |
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| PMID 9529257 |
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| PMID 9895331 |
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