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Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression

Mirna Mourtada-Maarabouni1, Lucy Kirkham, Farzin Farzaneh

  • 1School of Life Sciences, Keele University, Keele, ST5 5BG, UK. bia19@biol.keele.ac.uk

Oncogene
|November 16, 2004
PubMed

Insights

Researchers identified a gene sequence that suppresses T-cell apoptosis, offering resistance to cell death induced by various agents. This finding highlights the role of the fau gene in controlling critical cell death events.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Functional expression cloning is vital for discovering biological pathway components without prior assumptions.
  • Identifying molecules controlling apoptosis is crucial for understanding cell death mechanisms.
  • The fau gene, associated with FBR-MuSV, has reported tumor suppressor and oncogenic roles.

Purpose of the Study:

  • To identify genes involved in suppressing T-cell apoptosis using functional expression cloning.
  • To investigate the role of the fau gene in regulating apoptosis and cell survival.

Main Methods:

  • Functional expression cloning screen to identify apoptosis-suppressing sequences.
  • Isolation of a sequence antisense to the fau gene.
  • Assessment of apoptosis resistance induced by dexamethasone, UV radiation, and cisplatin.
  • Analysis of fau gene overexpression effects on cell death.

Main Results:

  • An antisense sequence to the fau gene was identified, suppressing endogenous fau mRNA.
  • This fau antisense sequence conferred resistance to apoptosis induced by dexamethasone, UV radiation, and cisplatin.
  • Colony-forming ability was protected, indicating fau's role in pre-commitment cell death events.
  • Overexpression of fau induced cell death, inhibited by Bcl-2 and caspase inhibitors.

Conclusions:

  • The fau gene plays a significant role in regulating apoptosis.
  • Modulating fau expression can influence cellular resistance to apoptosis-inducing agents.
  • Targeting fau may offer therapeutic strategies for diseases involving aberrant apoptosis.

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