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Updated: Dec 18, 2025

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.3K

NatB regulates Rb mutant cell death and tumor growth by modulating EGFR/MAPK signaling through the N-end rule

Zhentao Sheng1, Wei Du1

  • 1Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois, United States of America.

Plos Genetics
|June 20, 2020
PubMed

Insights

The N-terminal acetyltransferase B (NatB) complex promotes cancer cell survival by boosting EGFR/MAPK signaling. Inhibiting NatB may offer a new strategy for treating cancers driven by this pathway.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Signal transduction

Background:

  • The Rb tumor suppressor regulates cell proliferation and death.
  • Loss of Rb function can lead to either increased proliferation or cell death.
  • Identifying factors influencing Rb mutant cell fate is crucial for understanding cancer development.

Purpose of the Study:

  • To identify genetic factors promoting cell death in Rb-deficient Drosophila.
  • To investigate the role of N-terminal acetyltransferase B (NatB) in EGFR/MAPK signaling and cell survival.
  • To explore the therapeutic potential of targeting NatB in cancer.

Main Methods:

  • Conducted a genetic screen in Drosophila to identify genes involved in Rb mutant cell death.
  • Utilized molecular biology techniques to analyze the impact of NatB on EGFR/MAPK pathway components.
  • Investigated the role of specific E3 ubiquitin ligases (Ubr4, Cnot4) in NatB-mediated signaling modulation.

Main Results:

  • Identified Psid, a NatB subunit, as a key regulator of Rb mutant cell death.
  • Demonstrated that NatB is essential for elevated EGFR/MAPK signaling and Rb mutant cell survival.
  • Showed that NatB inversely regulates levels of positive (Grb2/Drk, MAPK) and negative (PP2AC) signaling components via N-end rule E3 ligases.

Conclusions:

  • NatB and N-end rule pathways interact to modulate EGFR/MAPK signaling through differential regulation of pathway components.
  • Psid inactivation inhibits EGFR signaling-dependent tumor growth.
  • NatB represents a potential therapeutic target for cancers reliant on deregulated EGFR/Ras signaling.

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