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Updated: Oct 13, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Inhibition of the mammalian transcription factor LSF induces S-phase-dependent apoptosis by downregulating

C M Powell1, T L Rudge, Q Zhu

  • 1Committee on Virology and Department of Microbiology and Molecular Genetics, Harvard Medical School and Division of Molecular Genetics, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

The EMBO Journal
|September 6, 2000
PubMed

Insights

LSF is a novel regulatory factor essential for DNA replication and cell survival. It targets the thymidylate synthase (TS) gene, and its inhibition leads to apoptosis, mimicking thymineless death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Thymidylate synthase (TS) is crucial for DNA replication and cell survival, induced during the G(1)-S phase transition.
  • LSF (LBP-1c, CP2) is a transcription factor implicated in cellular processes.

Purpose of the Study:

  • To investigate the role of LSF in regulating thymidylate synthase (TS) gene expression.
  • To determine if LSF is a novel regulatory factor involved in cell cycle progression and survival.

Main Methods:

  • Analysis of LSF binding sites within the TS promoter and intronic regions.
  • Site-directed mutagenesis of LSF binding sites in a TS minigene.
  • Expression of dominant-negative LSF (LSFdn) in mouse and human cell lines.
  • Assessment of TS enzyme levels, mRNA induction, and apoptosis.

Main Results:

  • LSF binds to critical regulatory regions of the TS gene promoter and introns.
  • Mutating LSF binding sites abrogates G(1)-S induction of TS mRNA.
  • Dominant-negative LSF (LSFdn) inhibits TS enzyme upregulation and induces apoptosis in growth-stimulated cells.
  • Apoptosis induced by LSFdn can be rescued by thymidine or TS gene re-expression.

Conclusions:

  • LSF is a novel regulatory factor essential for the G(1)-S transition and TS gene induction.
  • LSF plays a critical role in supporting S-phase progression by regulating TS.
  • LSF activity is vital for cell survival, and its inhibition mimics thymineless death.

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