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Updated: May 20, 2026
Mapping and Application of Enhancer-trap Flippase Expression in Larval and Adult Drosophila CNS
Published on: June 3, 2011
FLIP: a flop for execution signals
Kothandharaman Subramaniam1, Jayshree L Hirpara, Lisa Tucker-Kellogg
1Apoptosis, ROS and Cancer Biology Program, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract:
Resistance to apoptosis is one of the established hallmarks of cancer cells. This is a function of an imbalance between the proteins that facilitate death execution and those that inhibit apoptosis or promote cell proliferation. The anti-apoptotic protein, FLICE inhibitory protein (FLIP), first identified as a viral protein, is over-expressed in a variety of human pathologies. Initial observations linked FLIP expression to inhibition of death receptor induced apoptosis, due to its structural homology to the cysteine protease, caspase-8. FLIP impedes full processing of pro-caspase-8 to its active form and its release to the cytosol, and by doing so blocks apoptotic signaling downstream of the membrane death initiating signaling complex (DISC). Recent observations have highlighted the complex regulation of this protein and its cross talk with diverse signaling networks and metabolic processes. As FLIP expression is directly associated with chemotherapy resistance, a better understanding of its genomic organization, gene transcription, as well as post-transcriptional regulation could yield novel targets with potential therapeutic implications against drug refractory cancers. In this short review, we provide a brief overview of the structural and functional biology of this somewhat complex protein with direct relevance to carcinogenesis.
Insights
Cancer cells resist apoptosis due to an imbalance of cell death proteins, notably the over-expressed FLICE inhibitory protein (FLIP). Understanding FLIP
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Resistance to apoptosis is a key characteristic of cancer cells, often resulting from an imbalance between pro-death and anti-apoptotic proteins.
- The anti-apoptotic protein, FLICE inhibitory protein (FLIP), is over-expressed in various human pathologies and linked to cancer progression.
Purpose of the Study:
- To provide an overview of the structural and functional biology of FLIP.
- To highlight FLIP's role in carcinogenesis and its relevance to chemotherapy resistance.
Main Methods:
- Review of existing literature on FLIP's structure, function, and regulation.
- Analysis of FLIP's interaction with apoptotic pathways, particularly caspase-8.
- Exploration of FLIP's association with signaling networks and metabolic processes.
Main Results:
- FLIP inhibits apoptosis by impeding the processing of pro-caspase-8 within the death-initiating signaling complex (DISC).
- FLIP expression is associated with chemotherapy resistance in various cancers.
- FLIP exhibits complex regulation and crosstalk with diverse cellular signaling and metabolic pathways.
Conclusions:
- FLIP is a critical protein in carcinogenesis and a determinant of chemotherapy resistance.
- Further understanding of FLIP's genomic organization, transcription, and post-transcriptional regulation may reveal novel therapeutic targets for drug-refractory cancers.
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