Identification of a hTid‐1 mutation which sensitizes gliomas to apoptosis

Human Tid‐1 (hTid‐1) is a DnaJ chaperone protein with homology to the Drosophila tumor suppressor Tid56. We report the first case of a tumor‐associated mutation at the human TID1 locus, which was identified in the SF767 glioma cell line giving rise to aberrantly high levels of a hTid‐1L mutant variant. In this study, we set out to determine whether this change in hTid‐1 status influences the response of glioma cells to adenoviral (Ad)‐mediated delivery of the two major isoforms of TID1, hTid‐1L and hTid‐1S. Ad‐hTid‐1S induced apoptosis in hTid‐1 mutant SF767 cells, while causing growth arrest in wild‐type hTid‐1‐expressing U373 and U87 cells. By contrast, Ad‐hTid‐1L infection had no apparent effect on glioma cell growth. The apoptosis induced by hTid‐1S was accompanied by mitochondrial cytochrome C release and caspase activation and blocked by stable overexpression of Bcl‐XL. Our findings suggest that the status of hTid‐1 in gliomas may contribute to their susceptibility to cell death triggers.

Identification of a hTid‐1 mutation which sensitizes gliomas to apoptosis Journal Articles