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Updated: Aug 9, 2026
A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
Candidate tumour suppressor LUCA-15 can regulate multiple apoptotic pathways
M Mourtada-Maarabouni1, L C Sutherland, G T Williams
1School of Life Sciences, Keele University, Keele, ST5 5BG, UK.
Abstract:
Functional screening of a human bone marrow cDNA library for suppressors of CD95-mediated apoptosis has led to the identification of a 326 bp fragment (Je2), which not only suppresses CD95-induced apoptosis in Jurkat T-cells, but maps to 3p21.3, to an intronic region of the candidate TSG LUCA-15 locus. Here we report that overexpression of Je2 in CEM-C7 T-cell line is able to suppress CD95-mediated apoptosis, and apoptosis induced by TNFalpha and the glucocorticoid analogue dexamethasone, but was not able to suppress death induced by the topoisomerase II inhibitor etoposide. Je2 inhibition of apoptosis is also associated with a change in the pattern of expression of LUCA-15-encoded proteins. Je2 might therefore function to inhibit apoptosis by destabilising message expression of LUCA-15 and promoting the degradation of its RNA and protein. This suppression of apoptosis by Je2 also appears to be associated with up-regulation of the apoptosis inhibitory protein Bcl-x(L). This study confirms that Je2 is a selective inhibitor of cell death and further implicates LUCA-15 gene locus in the control of apoptosis.
Insights
A novel gene fragment, Je2, selectively inhibits apoptosis in T-cells by affecting the LUCA-15 gene locus and upregulating Bcl-x(L). This discovery offers new insights into controlling programmed cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- CD95-mediated apoptosis is a critical process in T-cell function and homeostasis.
- Identifying regulators of apoptosis is crucial for understanding cell death pathways and developing therapeutic strategies.
Purpose of the Study:
- To identify and characterize novel suppressors of CD95-mediated apoptosis.
- To investigate the functional role of the identified fragment (Je2) in regulating apoptosis and its association with the LUCA-15 gene locus.
Main Methods:
- Functional screening of a human bone marrow cDNA library.
- Overexpression of the Je2 fragment in CEM-C7 T-cell lines.
- Assessing apoptosis induction by various stimuli (CD95, TNFalpha, dexamethasone, etoposide).
- Analysis of LUCA-15 gene expression and Bcl-x(L) protein levels.
Main Results:
- A 326 bp fragment (Je2) was identified that suppresses CD95-mediated apoptosis in T-cells.
- Je2 overexpression inhibited apoptosis induced by CD95, TNFalpha, and dexamethasone, but not etoposide.
- Je2 expression altered LUCA-15 protein expression patterns and was associated with Bcl-x(L) upregulation.
- Je2 maps to an intronic region of the candidate tumor suppressor gene LUCA-15 at 3p21.3.
Conclusions:
- Je2 is a selective inhibitor of T-cell apoptosis.
- Je2 may function by destabilizing LUCA-15 mRNA and protein expression.
- The LUCA-15 gene locus is implicated in the control of apoptosis.
- Je2's anti-apoptotic activity is linked to Bcl-x(L) upregulation.
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