Recombinant Human NFkB p105 / p50 protein (GST tag N-Terminus)

일반 정보

기능

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.. Nuclear factor NF-kappa-B p105 subunit. P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B (PubMed : 1423592). Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105 (PubMed : 1423592).. Nuclear factor NF-kappa-B p50 subunit. Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor (PubMed : 1740106, PubMed : 7830764). Together with RELA/p65, binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions (PubMed : 1740106, PubMed : 7830764).

Post-translational modifications

Generation of the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) transcription factor takes place both cotranslationally and post-translationally via non-mutually exclusive mechanisms (PubMed:10970863, PubMed:25860612, PubMed:8628291, PubMed:9529257). A cotranslational processing allows the production of both p50 and p105 (Nuclear factor NF-kappa-B p105 subunit) from a single NFKB1 mRNA (PubMed:10970863, PubMed:8628291, PubMed:9529257). While translation occurs, the particular unfolded structure after the GRR repeat region acts as a substrate for the proteasome, promoting degradation of the C-terminus (PubMed:10970863, PubMed:9529257). The GRR acts as a proteasomal 'stop signal', protecting the region upstream of the GRR from degradation and promoting generation of p50 (PubMed:10970863, PubMed:9529257). It is unclear if limited proteasome degradation during cotranslational processing depends on ubiquitination (PubMed:10970863, PubMed:9529257). NF-kappa-B p50 is also generated post-translationally following ubiquitination by the KPC complex, leading to limited processing by the proteasome downstream of the GRR region, thereby generating p50 (PubMed:25860612).. Nuclear factor NF-kappa-B p105 subunit. Phosphorylation at the C-terminus by IKBKB/IKKB acts as a signal for ubiquitination and promotes either complete degradation or processing to generate the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:10835356, PubMed:11158290, PubMed:11297557, PubMed:12482991, PubMed:14673179, PubMed:25860612, PubMed:8626394). Phosphorylation at Ser-903 and Ser-907 primes p105 for proteolytic processing in response to TNF stimulation (PubMed:12871932). Phosphorylation at Ser-923, Ser-927 and Ser-932 are required for BTRC/BTRCP-mediated ubiquitination and proteolysis (PubMed:10835356, PubMed:11158290, PubMed:11297557, PubMed:12482991, PubMed:14673179). Phosphorylation at Ser-927 is also required for ubiquitination by the KPC complex and limited processing to generate NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:25860612).. Nuclear factor NF-kappa-B p105 subunit. Polyubiquitinated at multiple Lys residues in the C-terminus (PubMed:11158290, PubMed:14673179, PubMed:25860612). Polyubiquitinated by the SCF(FBXW11) and SCF(BTRC) complexes following phosphorylation at Ser-923, Ser-927 and Ser-932, leading to its complete degradation (PubMed:11158290). In contrast, polyubiquitination by the KPC complex following phosphorylation at Ser-927 leads to limited proteosomal processing and generation of the active NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (PubMed:25860612).. S-nitrosylation of Cys-61 affects DNA binding.. The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.