0000000000729799
AUTHOR
Gerd Helftenbein
Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals
Claudin-18 isoform 2 (CLDN18.2) is one of the few members of the human claudin family of tight junction molecules with strict restriction to one cell lineage. The objective of the current study was to compare molecular structure and tissue distribution of this gastrocyte specific molecule in mammals. We show here that the CLDN18.2 protein sequence is highly conserved, in particular with regard to functionally relevant domains in mouse, rat, rabbit, dog, monkey and human and also in lizards. Moreover, promoter regions of orthologs are highly homologous, including the binding site of the transcription factor cyclic AMP-responsive element binding protein (CREB), which is known to regulate acti…
In silico strategy for detection of target candidates for antibody therapy of solid tumors
In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from …
Identification of new claudin family members by a novel PSI-BLAST based approach with enhanced specificity.
In an attempt to develop a novel strategy for the identification of new members of protein families by in silico approaches, we have developed a semi-automated procedure of consecutive PSI-BLAST (Position-Specific-Iterated Basic Local Alignment Search Tool) searches incorporating identificiation as well as subsequent validation of putative candidates. For a proof of concept study we chose the search for novel members of the claudin family. The initial step was an iterated PSI-BLAST search starting with the PMP22_Claudin domain of each known member of the claudin family against the human part of the RefSeq Database. Putative new claudin domains derived from the converged list were evaluated …