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Updated: Mar 21, 2026

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
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praja2 regulates KSR1 stability and mitogenic signaling

L Rinaldi1, R Delle Donne1, M Sepe1

  • 1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, IEOS-CNR, CEINGE University Federico II, Naples 80131, Italy.

Cell Death & Disease
|May 20, 2016
PubMed

Insights

The kinase suppressor of Ras 1 (KSR1) is degraded via ubiquitination, a process regulated by praja2. This mechanism controls ERK signaling, impacting cell proliferation and stem cell pluripotency.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Kinase suppressor of Ras 1 (KSR1) is crucial for Ras/MAP kinase pathway signaling.
  • KSR1 scaffolds signaling components to activate ERK, a key mitogenic pathway.
  • Regulation of KSR1 stability is essential for controlling cellular responses.

Purpose of the Study:

  • To elucidate a novel mechanism for ERK pathway attenuation.
  • To identify the E3 ligase responsible for KSR1 degradation.
  • To investigate the role of KSR1 ubiquitination in cancer cell growth and stem cell pluripotency.

Main Methods:

  • Studied KSR1 polyubiquitination upon growth factor stimulation.
  • Identified praja2 as the E3 ligase targeting KSR1.
  • Assessed the impact of praja2-dependent KSR1 regulation on ERK signaling, cancer cell proliferation, and embryonic stem cell pluripotency.

Main Results:

  • Hormone or growth factor stimulation induced KSR1 polyubiquitination, correlating with decreased ERK1/2 signaling.
  • Praja2 was identified as the E3 ligase responsible for KSR1 ubiquitination.
  • Praja2-mediated regulation of KSR1 influences cancer cell growth and maintains the pluripotent state of mouse embryonic stem cells.

Conclusions:

  • Ubiquitin-dependent proteolysis of KSR1 represents a novel mechanism for ERK pathway attenuation.
  • Praja2 plays a critical role in regulating KSR1 levels and downstream signaling.
  • The interplay between ubiquitination and KSR1 scaffolding impacts cell proliferation and stem cell pluripotency, offering potential therapeutic targets.

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