Identification of a hTid-1 mutation which sensitizes gliomas to apoptosis.

Abstract:

: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-1(L) 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-1(L) and hTid-1(S). Ad-hTid-1(S) 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-1(L) infection had no apparent effect on glioma cell growth. The apoptosis induced by hTid-1(S) was accompanied by mitochondrial cytochrome C release and caspase activation and blocked by stable overexpression of Bcl-X(L). Our findings suggest that the status of hTid-1 in gliomas may contribute to their susceptibility to cell death triggers.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Trentin GA,He Y,Wu DC,Tang D,Rozakis-Adcock M

doi

10.1016/j.febslet.2004.11.034

keywords:

subject

Has Abstract

pub_date

2004-12-17 00:00:00

pages

323-30

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(04)01415-2

journal_volume

578

pub_type

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