Disease relevance of NFKBIL1

• Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL [1].

High impact information on NFKBIL1

• BACKGROUND & AIMS: IKBL gene lies telomeric of the tumor necrosis factor cluster in the central major histocompatibility complex and carries a structural polymorphism at position +738 [1].
• We show that a subset of serine/arginine (SR)-rich proteins activate a cryptic 3' splice site in a sense Alu repeat located in intron 4 of the human LST1 gene [2].
• The LST1 transcripts are expressed at high levels in dendritic cells [3].
• The gene for the human leukocyte-specific transcript 1 (LST1) encodes a small protein that modulates immune responses and cellular morphogenesis [3].
• Because of the complex splicing pattern, use of alternative 5'-untranslated exons, and a biologically interesting pattern of expression of LST1 mRNA, we studied the human LST1 gene promoter and regulatory elements [3].

Biological context of NFKBIL1

• Direct determination of single nucleotide polymorphism haplotype of NFKBIL1 promoter polymorphism by DNA conformation analysis and its application to association study of chronic inflammatory diseases [4].
• In addition, the frequency of IKBLp*01, but not that of other -63T-bearing alleles, was increased in the patients with RA (73.3% vs 58.1%, giving an odds ratio of 1.99), suggesting that the susceptibility to RA was conferred not by -63T alone but by combination of single nucleotide polymorphisms in the NFKBIL1 promoter [4].
• Similarly, attempts to correlate SNP at the NcoI-RFLP within intron 1 of the TNFB, IKBL and TLR4 gene with UVB phenotypes also failed [5].
• Transient transfections of luciferase reporter constructs carrying promoter alleles of IKBL into Jurkat cells showed an effect of IKBL-62 alleles [6].
• IKBL encodes a protein resembling members of the IkappaB protein family that regulate bioavailability of NFkappaB [6].

Anatomical context of NFKBIL1

• IKBL was expressed at low levels in Jurkat cells but not in blood mononuclear cells, and expression declined following mitogenic stimulation [6].
• The restriction of IKBL expression to Jurkat cells is consistent with evidence that E47 is expressed in thymocytes and suggests IKBL may affect autoimmunity through an effect on T-cell selection [6].
• Transfection of B144/LST1 into a variety of cells induces morphologic changes including the production of long, thin filopodia differing from those seen on transfection of a dominant active CDC42 gene [7].
• These data suggest that LST1 may have a specific role in monocytes and possibly also in T cells [8].

Associations of NFKBIL1 with chemical compounds

• When subjects expressing DRB 1*501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL [9].
• Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of kappa B-like protein (IKBL) [9].
• Interestingly, translation of IkappaBL mRNA in vivo was found to initiate predominantly from the second available methionine, thereby resulting in the disruption of the predicted N-terminal PEST sequence [10].
• Blockade of the NTCP, OATP1-3, and LST-1 transporters with 10 mM sodium taurocholate did not alter the deiodination rate of T4 by Cys133D2 transiently expressed in intact cells, suggesting that intracellular transport of T4 is not rate limiting [11].

Other interactions of NFKBIL1

• In each DNA sample, we established the genotype of 25 microsatellite markers distributed throughout the HLA region, that of single nucleotide polymorphism within the 5'-flanking regions of the TNFA and IkBLI (also known as NFKBIL1) as well as HLA class I and II genes [12].
• A promoter polymorphism in the central MHC gene, IKBL, influences the binding of transcription factors USF1 and E47 on disease-associated haplotypes [6].

Analytical, diagnostic and therapeutic context of NFKBIL1

• In the IKBL gene a predisposing allele was identified (13.1% vs 7.5% in the control group, P < 0.001) [13].

References