SEL1L a multifaceted protein playing a role in tumor progression

Since the cloning in 1997 of SEL1L, the human ortholog of the sel‐1 gene of C. elegans, most studies have focused on its role in cancer progression and have provided significant evidences to link its increased expression to a decrease in tumor aggressiveness. SEL1L resides on a “Genome Desert area” on chromosome 14q24.3‐31 and is highly conserved in evolution. The function of the SEL1L encoded protein is still very elusive although, several evidences from lower organisms indicate that it plays a major role in protein degradation using the ubiquitin‐proteosome system. SEL1L has a very complex structure made up of modules: genomically it consists of 21 exons featuring several alternative transcripts encoding for putative protein isoforms. This structural complexity ensures protein flexibility and specificity, indeed the protein was found in different sub‐cellular compartments and may turn on a particular transcript in response to specific stimuli. The overall architecture of SEL1L guarantees an exquisite regulation in the expression of the gene. © 2005 Wiley‐Liss, Inc.