Disease relevance of Lancl1

• Macrophages and DC from these mice faithfully reported biallelic p40 induction using the fluorescent marker. s.c. inoculation with Listeria monocytogenes or LPS led to a rapid, but transient, accumulation of p40-expressing DC in draining lymph nodes, which could be blocked by the addition of pertussis toxin [1].
• The nucleotide sequence of a cDNA that encodes a new regulatory subunit, named p40, of the 26S proteasome of human hepatoblastoma HepG2 cells has been determined [2].

High impact information on Lancl1

• Consistent with the in vivo findings, in vitro-activated DC that expressed p40 migrated to draining lymph nodes and promoted Th1 differentiation more efficiently than DC that did not express p40 [1].
• In situ analysis also revealed the accumulation of IL-12p40 protein around high endothelial venules located in close proximity to p40-expressing DC [1].
• In an effort to understand the location and kinetics of these cytokines during the course of an immune response, we generated knockin (gene-targeted) mice that express the p40 gene linked via a viral internal ribosome entry site element with fluorescent reporters, eYFP or eGFP [1].
• This result is in striking contrast to the proposed seven-transmembrane protein structure and function and therefore we wish to correct our previous proposal. p40 is located at the cytoplasmic side of the membrane and is neither associated with the cytoskeleton nor lipid rafts [3].
• Therefore, we rename p40 to LanC-like protein 1 (LANCL1) and suggest that it may play a similar role as a peptide-modifying enzyme component in eukaryotic cells [3].

Biological context of Lancl1

• We have determined the organization and chromosome location of the human LANCL1 and mouse Lancl1 genes encoding LANCL1, the lanthionine synthetase component C (LanC)-like protein 1 [4].
• Fluorescence in situ hybridization analyses assigned the LANCL1 gene to human chromosome 2q34 and the Lancl1 gene to mouse chromosome 1, region C2-C5, in accordance with the known homology [4].

Associations of Lancl1 with chemical compounds

• LANCL1 (LanC-like protein 1) is related to the bacterial LanC (lanthionine synthetase C) family, which is involved in the biosynthesis of antimicrobial peptides [5].
• A KEKE motif, consisting of a very hydrophilic domain rich in 'alternating' lysine (positive) and glutamate (negative) residues, is present in the C-terminus of p40 [2].

Analytical, diagnostic and therapeutic context of Lancl1

• Refined sequence analysis revealed that p40 is related to the LanC family of bacterial membrane-associated proteins which are involved in the biosynthesis of antimicrobial peptides [3].
• Similar results were obtained using a p40 subunit-specific enzyme-linked immunosorbent assay [6].

References