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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Using the E1A Minigene Tool to Study mRNA Splicing Changes

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A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine

Valerie Edmond1, Galina Merdzhanova, Stephanie Gout

  • 1INSERM, U823, Equipe 2 Bases Moléculaires de la Progression des Cancers du Poumon, Grenoble, France.

Cell Cycle (Georgetown, Tex.)
|March 23, 2013
PubMed

Insights

The SR protein SRSF2 promotes cell cycle progression by interacting with E2F1 in lung cancer. Inhibition of AKT signaling blocks SRSF2 phosphorylation and its function in E2F1 transcriptional activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • E2F1 is a transcription factor vital for cell cycle and apoptosis.
  • SRSF2 is an RNA-binding protein regulating pre-mRNA splicing.
  • E2F1 and SRSF2 cooperate in apoptosis induction in lung cancer.

Purpose of the Study:

  • To investigate the role of SRSF2 in the proliferative functions of E2F1.
  • To explore the link between SRSF2, E2F1, and cell cycle progression in lung tumors.

Main Methods:

  • Immunohistochemistry (IHC) to detect SRSF2 and P-SRSF2 expression.
  • Correlation analysis between cyclin E and P-SRSF2 levels.
  • Cell cycle analysis in neuroendocrine lung carcinoma cell lines.
  • Investigation of SRSF2-E2F1 interaction and AKT signaling inhibition.

Main Results:

  • SRSF2 and P-SRSF2 are overexpressed in proliferative neuroendocrine lung tumors with high E2F1.
  • A significant correlation exists between cyclin E and P-SRSF2 levels, indicating a role in proliferation.
  • SRSF2 is cell cycle-regulated, essential for S phase entry and progression.
  • SRSF2 interacts with E2F1, enhancing its transcriptional control of cell cycle genes.
  • AKT inhibition reduces SRSF2 phosphorylation and its activity on E2F1.

Conclusions:

  • SRSF2 plays a novel role in controlling cell cycle progression.
  • A functional link between SRSF2 and E2F1 in cell proliferation is reinforced.
  • SRSF2's activity is regulated by AKT signaling in the context of E2F1 function.
Keywords:
AKTE2F1SRSF2cellular proliferationneuroendocrine lung tumorsp45SKP2

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