tailieunhanh - Báo cáo khoa học: A novel splice variant of occludin deleted in exon 9 and its role in cell apoptosis and invasion

The tight junction protein occludin participates in cell adhesion and migra-tion and has been shown to possess antitumorigenic properties; however, the exact mechanism underlying these effects is poorly understood. In liver cell lines, we identified an occludin splice variant deleted in exon 9 (Occ DE9 ). | ỊFEBS Journal A novel splice variant of occludin deleted in exon 9 and its role in cell apoptosis and invasion Jin-Mo Gu1 Seung Oe Lim1 Young Min Park2 and Guhung Jung1 1 Department of BiologicalSciences and SeoulNationalUniversity Korea 2 Hepatology Center and Laboratory of Hepatocarcinogenesis Bundang Jesaeng General Hospital Kyungkido Korea Keywords apoptosis calcium invasion occludin splice variant Correspondence G. Jung Department of Biological Sciences and SeoulNationalUniversity 56-1 Shillim-dong Kwanak-gu Seoul151-747 Korea Fax 82 2 872 1993 Tel 82 2 880 7773 E-mail drjung@ Received 18 February 2008 revised 11 April 2008 accepted 15 April 2008 doi The tight junction protein occludin participates in cell adhesion and migration and has been shown to possess antitumorigenic properties however the exact mechanism underlying these effects is poorly understood. In liver cell lines we identified an occludin splice variant deleted in exon 9 OccAE9 . Furthermore comparison analysis of wild-type occludin OccWT and OccAE9 revealed that exon 9 played important roles in the induction of mitochondria-mediated apoptosis and the inhibition of invasion along with the downregulation of matrix metalloproteinase expression. In addition by using the calcium indicator X-rhod-1 and the inositol trisphosphate receptor inhibitor 2-aminoethoxydiphenyl borate we found that OccWT but not OccAE9 increased calcium release from the endoplasmic reticulum. In conclusion our results showed that occludin mediates apoptosis and invasion by elevating the cytoplasmic calcium concentration and that exon 9 of occludin is an important region that mediates these effects. Occludin is a tight junction TJ protein and the first identified TJ-associated molecule 1 . Occludin is the product of a single gene located on human chromosome band and produces several different mRNAs as a result of alternative splicing 2 . Recently several variants of occludin .